• Psychedelic Medicine

EPILEPSY | +50 articles

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CBD treatment for epilepsy does not adversely effect memory*

by Eric Dolan | PsyPost | 20 Feb 2021

Treatment with highly purified cannabidiol among epilepsy patients is associated with increases in neural activity in prefrontal brain regions related to verbal memory and attention, according to new research published in Epilepsy & Behavior. But the treatment does not appear to significantly impact working memory performance.

“We were interested in better understanding highly purified CBD’s effects on working memory for several reasons,” said study author Tyler Gaston of the University of Alabama at Birmingham.

“First and foremost, with the FDA approval of Epidiolex, neurologists who may prescribe this medication for their epilepsy patients need to know if there are any untoward effects on memory that could be attributed to the medication. This is important because people with epilepsy already can suffer from memory difficulties.”

“Further, there have been some documented negative effects of other cannabis products on cognition,
" Gaston said. “We wanted to determine if purified CBD had any effects such as this.”

In the study, the researchers examined the brain activity of 20 patients with treatment-resistant epilepsy prior to initiation of CBD treatment and after reaching a stable dosage. Gaston and his colleagues also recruited 23 healthy volunteers, who served as a control group.

“Our study used a tool called functional MRI (fMRI) to look at changes in brain activity as a result of starting treatment with CBD. The participants did a working memory task while they were being scanned, and this is how we can determine any changes or differences in neural activity for working memory,” Gaston explained.

As expected, working memory performance tended to be worse among the epilepsy patients compared to the control group. The researchers also found no evidence that CBD treatment resulted in significant changes in working memory performance. But they did observe increases in activation of the inferior frontal gyrus and insula after CBD treatment.

The findings provide some preliminary evidence that may CBD can help to “normalize” attentional and memory processing.

“Purified CBD does not have a significant effect either positively or negatively on working memory performance in people with epilepsy. We did, however, note that after CBD treatment that there some increases in brain activity in regions of the brain important for verbal memory and attention,” Gaston told PsyPost.

The study — like all research — includes some limitations.

“There were several things we could not control for in our study, including type of epilepsy, number and type of other seizure medications taken, and some variability in the dose of CBD taken by participants at the time of their follow up fMRI,” Gaston explained. “Therefore, we cannot comment on whether any of these specific aspects may influence the effects of CBD on working memory and fMRI activity. Our study also just investigated adult patients, it will be helpful in the future to investigate if there are differences in brain activity in adolescents and children.”

“It is important to note that these data/results can only be applied to the FDA-approved product which is highly purified CBD, and cannot be extrapolated to other cannabis products,”
he added.

*From the article here :
 
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Specific set of nerve cells found to control seizures' spread through the brain*

Stanford Medicine | Science News | 15 Feb 2018

Experimental activation of a small set of nerve cells in the brain prevents convulsive seizures in a mouse model of temporal lobe epilepsy, the most common form of epilepsy among human adults.

Experimental activation of a small set of nerve cells in the brain prevents convulsive seizures in a mouse model of temporal lobe epilepsy, the most common form of epilepsy among human adults, according to a study by researchers at the Stanford University School of Medicine.

In contrast, inactivating these cells, known to neuroscientists as mossy cells, facilitates the spread throughout the brain of the electrical hyperactivity initially localized at a seizure's onset, causing the full-blown behavioral symptoms of temporal lobe epilepsy.

Inactivating this nerve-cell population also induces the same cognitive losses that characterize chronic, drug-resistant temporal lobe epilepsy in humans, the scientists found.

Epilepsy affects 65 million people worldwide, with 150,000 new cases diagnosed annually in the United States alone. Three out of five of those affected suffer from temporal lobe epilepsy. Progressive loss of mossy cells is a hallmark of this disorder.

Mossy cells are known to be damaged easily as a result of head trauma and decreased blood supply. Such brain injuries, in turn, increase the risk for temporal lobe epilepsy.

The role of mossy cells in epilepsy has perplexed neuroscientists for a couple of decades. The new Stanford study, which will be published Feb. 16 in Science, offers an explanation. And it points to an entirely new entry point for developing drugs that could bring therapeutic relief to people with chronic, drug-resistant epilepsy, a debilitating condition that not only circumscribes patients' lifestyles and occupational options but predisposes them to depression, anxiety and early death.

"It should, in principle, be possible to develop targeted therapies directed at mossy cells to control both seizures and the resulting cognitive deficits," said Ivan Soltesz, PhD, professor and vice chair of neurosurgery and the senior author of the study. "This would be great, because the 20 or more compounds now approved for treating patients fail 30 to 40 percent of the time."

The study's lead author is Soltesz's former graduate student, Anh Bui, PhD, now a medical student at the University of California-Irvine.

An electrical storm in the brain

Epileptic seizures are sometimes described as an electrical storm in the brain. These storms typically begin at a single spot in the brain, called the focus, where nerve cells -- for reasons that remain unclear -- begin repeatedly firing in synchrony. All too often they spread from the focus to widespread areas throughout the brain, a process called generalization. It's this brainwide hyperactivity that causes the classic behavioral symptoms of epileptic seizures, such as loss of consciousness, convulsions and disordered thinking.

The exact location of the epileptic focus in the brain varies from individual to individual. In the great majority of patients with temporal lobe epilepsy, the focus lies in the hippocampus, a much-studied, seahorse-shaped midbrain structure that's crucial to spatial navigation and to encoding new experiences into long-term memory.

Mossy cells, found exclusively in one section of the hippocampus, are few in number, but each connects with tens of thousands of other hippocampal nerve cells. Via these connections, mossy cells can stimulate a multitude of excitatory hippocampal nerve cells, whose output extends to other sections of the hippocampus. But they can also stimulate an opposing class of cells that inhibit these excitatory cells. Whether the net effect of mossy-cell activity is to promote or counter overall output of the excitatory nerve cells has, until now, been an open question.

To answer the question, Soltesz, who holds the James Doty Professorship of Neurosurgery and Neurosciences, and his colleagues turned to a mouse model of temporal lobe epilepsy.

The mice the Stanford investigators used were bioengineered so that their mossy cells responded to pulses of light, conveyed to those cells via an implanted optical fiber. Blue light caused mossy cells to fire, while amber light caused them to resist firing. So, by flipping a laser switch, the scientists could activate or inhibit the mice's mossy cells at will. (This increasingly widespread experimental technique, called optogenetics, is noteworthy for its capacity to target specific sets of nerve cells in order to reveal their function.) The scientists also recorded activity in the hippocampal region where mossy cells reside.

Effects of inhibiting, exciting mossy cells

Soltesz, Bui and their colleagues showed that inhibiting mossy cells, while not increasing the frequency of spontaneous episodes of hyperactivity in the focus of the chronically epileptic mice, did lead to a substantial increase in the number of seizures that spread from the focus to larger areas of the brain. Conversely, excitation of mossy cells in these mice diminished the number of generalized, outwardly visible seizures while having no effect, or merely a minor one, on the frequency of purely focal seizures.

In a memory test that gauges a mouse's recognition of unfamiliar objects, the epileptic mice, despite having lost more than half of their mossy cells, did fine. But they failed another test that assesses their ability to notice when a familiar object has been moved -- a gauge of spatial memory, which suffers a decline in chronic temporal lobe epilepsy. When the Stanford scientists also subjected optogenetically engineered but otherwise normal mice to these tests, they did great -- until the researchers inhibited their mossy cells, at which point these animals' spatial recall headed south, too.

"We've shown that mossy cells' role is protective in preventing the spread to other brain regions of seizures that originate in the hippocampus, the dominant focal site for seizures associated with temporal lobe epilepsy," said Soltesz. "Drugs targeting mossy cells in patients with chronic, drug-resistant cases may someday be able to reduce the incidence of convulsive seizures enough to give patients' back some of their lost lifestyles."

"Such interventions might serve as an alternative to demanding surgical procedures now employed to excise the seizure focus from patients' brains,"
Soltesz said.

*From the article here :
 
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‘Life-changing’ impact of medical cannabis in epilepsy patients revealed

by Sarah Sinclair | Cannabis Health News | 15 Dec 2020

A new report has revealed the ‘remarkable’ and ‘life-changing’ impact of medical cannabis on ten patients with severe epilepsy.

The study, published by Drug Science, followed ten patients, aged two to 48-years-old, with intractable, childhood onset epilepsies. It found that patients saw an average 97 percent reduction in seizures following treatment with cannabis medicines.

Four patients, who were prescribed Epidiolex, a licensed cannabis medicine in the UK, did not see any improvement in their condition until they were given the whole plant extract – suggesting a combination of CBD and THC based products was crucial in effectively managing the condition.

The carers of patients provided details of their age, diagnosis, previous and current antiepileptic drugs and number of seizures before and after taking cannabis based medicines, through the campaign group End our Pain. This data was then analysed by researchers at Drug Science.

As well as the clear improvement in their condition, the report also highlights the staggering financial barriers facing patients, with the average monthly cost of cannabis medicines more than £1,800.

Those families included in the study spend more than £20,000 a year on their children’s medicines – almost five times the price of the same medication in the Netherlands.

Lead author Rayyan Zafar told Cannabis Health: “The aim was to provide a scientific platform to convey the impact that medical cannabis treatment has had on children suffering from various forms of severe epilepsies. We wanted to assess primarily what the effects were on their seizure frequency as well as highlighting the extremely high costs of private prescriptions.”

He continued: “We saw a dramatic 97 percent average reduction across the cohort in seizure frequency following treatment with medical cannabis. These effects were seen using whole-plant extracts which combine THC and CBD therapy, which is not currently a National Institute for Health and Care Excellence (NICE) recommended treatment."

“Surprisingly the four patients that had the NICE recommended Epidiolex did not improve on this longer term and only saw beneficial effects once whole plant extracts were taken.”


Researchers conclude that the impact of cannabis medicines on these patients was ‘remarkable’ and often ‘life-changing’ and argue that the paper provides important evidence that should be taken into account, in addition to RCTs.

Dr Anne Katrin Schlag, head of research at Drug Science, said: “We think our findings make a very strong case for prescribing these medicines to this group of children and young adults who have been clearly shown to benefit from it."

“We are currently following up with a subsection of patients who for cost reasons, had to discontinue their medications, leading to their seizures returning, adding further validity to the current findings."

“We hope our report will contribute to make access to these medicines easier, and to allow for medicinal cannabis to become accessible on the NHS for these patients who are shown to benefit from it.”


Although randomised controlled trials (RTCs) are recommended to provide clinical evidence on the efficacy of unlicensed cannabis medicines, it would be ‘extremely difficult’ to conduct these in very ill patients, according to the report.

Those already taking cannabis medicines would be required to undergo a ‘wash out’ period to come off their current medication and run the risk of being given a placebo, which parents have warned could put their lives at risk.

“Whilst the paper has been received with great interest, we expect responses will also call for greater sample sizes, which we are in the process of doing, and the application of RCTs,” added Zafar and Dr Schlag.

“However, RCTs in these children suffering from severe epilepsies would be unethical and highly costly.”

Campaigner Hannah Deacon, whose son Alfie Dingley is one of a handful of patients to have an NHS prescription for medical cannabis – and who continues to support others to get access – welcomed the report, saying it must be accepted as evidence.

“It is clear from this study that whilst some doctors may believe medical cannabis is something to be frightened of, it is quite the contrary. These patients are having reduced seizures – sometimes none for days on end – and a hugely improved quality of life. This is evidence and must be accepted as such,” she said.

“The families who spend every day raising money to keep their children safe are in fact saving the NHS huge sums of money every day by keeping their children safe at home. I am tired of seeing this medicine blocked every day by different people who should be putting patients and their wellbeing at the centre of everything they do."

“It is time that we see safe access for these families and the many millions more in the UK.”


Professor Mike Barnes, who obtained the first license to prescribe medical cannabis in the UK, added that it was time others in the profession ‘embraced’ cannabis as a medicine.

He commented: “This paper shows the real efficacy of cannabis for children with epilepsy. Isn’t it now time for the paediatric neurology community to embrace this medicine and start to prescribe rather than hounding those that do.”

 
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Researchers propose system that delivers seizure forecasts, similar to weather forecasts,
offering predictions of when a person is a greater risk of seizure.


Brain implant forecasts seizures days in advance

by Rich Haridy | New Scientist | 20 Dec 2020

An international study is showing, for the first time, that it may be possible to predict the onset of epileptic seizures several days in advance. By analyzing data from a clinically approved brain implant designed to monitor and prevent seizures, the new research hopes to develop a model offering patients with epilepsy a seizure forecasting tool to predict the likelihood of upcoming episodes.

The research looked at data from a responsive brain stimulation implant called NeuroPace. The device was approved for clinical uses back in 2013 and it works to prevent seizures by delivering imperceptible pulses of electrical stimulation to certain parts of the brain upon detecting abnormal brain activity.

Scientists have been working on a variety of seizure prediction tools for decades. But despite some incredible advances, such as the NeuroPace device, no innovation to date has successfully shown it possible to predict seizures more than a few minutes in advance, at best.

The NeuroPace innovation offers researchers the first chance to study the relationship between seizures and brain activity using years of EEG data. The new study initially analyzed long-term data from 18 patients with the brain implant who were closely tracked for several years. From this data the researchers developed predictive algorithms to forecast seizures. These predictive algorithms were then tested on long-term data gathered from the more than 150 people who participated in the decade-long clinical trials testing the brain implant system.

Vikram Rao, co-senior author on the new study, says the data shows seizure risk could be effectively forecasted three days ahead in nearly 40 percent of subjects and one day ahead in 66 percent of subjects.

"For forty years, efforts to predict seizures have focused on developing early warning systems, which at best could give patients warnings just a few seconds or minutes in advance of a seizure,” says Rao. “This is the first time anyone has been able to forecast seizures reliably several days in advance, which could really allow people to start planning their lives around when they're at high or low risk.”

Rao does stress the current algorithm can only predict when one is at higher risk of seizure, and not specifically when a seizure will take place. A number of other unaccounted environmental triggers, from stress to erratic sleep, can play a role in the onset of a seizure. So the system currently developed is more like a weather forecast, offering probabilities designed to help guide a person’s future activities.

"I don't think I'm ever going to be able to tell a patient that she is going to have a seizure at precisely 3:17 pm tomorrow—that's like predicting when lightning will strike," explains Rao. "But our findings in this study give me hope that I may someday be able to tell her that, based on her brain activity, she has a 90 percent chance of a seizure tomorrow, so she should consider avoiding triggers like alcohol and refrain from high-risk activities like driving."

Much more work is needed before the system is ready for clinical use. This preliminary study uncovered a significant amount of variability from person to person. It is unclear why reliable forecasting could not be generated from some patient’s brain activity data. Future investigations to optimize the algorithm and perhaps incorporate multimodal physiological data may enhance the algorithm’s predictive capacity.

Plus, currently the system requires data gathered from a device requiring surgical implantation. This would limit the use of the device to only those with the most severe forms of epilepsy. More superficial subscalp EEG devices could offer a less invasive way of capturing this brain activity data over long periods of time.

"It is worth remembering that, currently, patients have absolutely no information about the future—which is like having no idea what the weather tomorrow might be—and we think our results could help significantly reduce that uncertainty for many people," adds Rao. "Truly determining the utility of these forecasts, and which patients will benefit most, will require a prospective trial, which is the next step."

The new study was published in the journal The Lancet Neurology.

 
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New dietary treatment for Epilepsy reduced seizures

UCL | Neuroscience News | 24 Jul 2021

K.Vita, a new oral dietary substance based on the ketogenic diet, reduced seizures by up to 50% in children and adults with drug-resistant epilepsy.

The first clinical trial of a new dietary treatment for children and adults with severe forms of epilepsy, co-developed by UCL researchers and based on the ketogenic diet, has been successfully completed.

For the study, published in Brain Communications, clinicians evaluated the use of K.Vita®, (also known as Betashot), an oral liquid dietary supplement developed by UCL in collaboration with Royal Holloway, University of London, and Vitaflo International Ltd.

The ketogenic diet (KD) consists of high-fat, low-carbohydrate and adequate protein consumption and mimics the fasting state, altering the metabolism to use body fat as the primary fuel source. This switch from carbohydrates to fat for body fuel is known as ketosis.

It is widely used to treat drug resistant epilepsies. However, the highly restrictive diet, which can cause constipation, low blood sugar, and stomach problems, can have poor compliance and is not suitable for everyone. Some KD supplements are also known to be unappetising.

K.Vita is based on novel findings by UCL researchers*, who discovered a different underlying mechanism to explain why the KD is effective against epilepsy; in developing a new treatment, researchers also sought to reduce the adverse side effects caused by KD.

Corresponding author Professor Matthew Walker (UCL Queen Square Institute of Neurology) said: “The ketogenic diet has been used for 100 years to treat epilepsy, helping reduce seizures in both children and adults."

“It has long been thought the diet was effective due to its production of ketones,
however we now believe the increase in levels of the fatty acid, decanoic acid, also produced by the diet, may provide the powerful antiseizure effects.

“In this study we evaluated a newly developed medium chain triglyceride (type of dietary fat) supplement, designed to increase levels of decanoic acid, while also reducing the adverse side effects, and to be more palatable.”

For the feasibility trial, researchers wanted to establish participants’ tolerance (side effects such as bloating or cramps) to the treatment, acceptability (flavour, texture, taste) and compliance (how easy it is to use K.Vita at the advised quantity, as part of their daily diet).

As secondary outcomes, they also monitored the frequency of epileptic seizures or paroxysmal events (fits, attacks, convulsions) and whether ketone production was decreased.

In total, 35 children aged 3 to 18 with genetically caused epilepsy and known to be unresponsive to drugs, and 26 adults with drug-resistant epilepsy (DRE), were given K.Vita liquid supplements (a drink), to be taken with meals. They were also asked to limit high-refined sugary food and beverages from their diets.

The trial lasted 12 weeks with K.Vita treatments increasing incrementally over time, taking into account individuals’ tolerance to the treatment.

In total, 23/35 (66 percent) of children, and 18/26 (69 percent) of adults completed the trial i.e they were continuing to take K.Vita at 12 weeks. Gastrointestinal disturbances were the primary reason for discontinuation, and their incidence decreased over time

Over three-quarters of participants/caregivers reported favourably on sensory attributes, such as taste, texture and appearance, and ease of use.

In regards to the secondary outcomes, there was a mean 50% reduction in seizures or paroxysmal events, and fewer than 10% of people on the diet produced significant ketones.

Commenting on the findings, Professor Walker, who is also a consultant neurologist at the National Hospital for Neurology and Neurosurgery, said: “Our study provides early evidence of the tolerability and effectiveness of a new dietary supplement in severe drug-resistant epilepsies in adults and children and provides a further treatment option in these devastating conditions."

“It also offers an alternative, more liberal, diet for those who cannot tolerate or do not have access to ketogenic diets.”


He added: “While this study was not designed to include enough patients to fully assess the supplement’s effects on seizures, it is exciting to report that there was a statistically significant reduction in the number of seizures in the group overall after three months of treatment."

“Furthermore, high ketone levels were not observed in over 90% of the participants. This indicates that the effect of the diet was independent from ketosis; this is important because high ketone levels in the ketogenic diets contribute to both short- and longer-term side effects.”


First author, Dr Natasha Schoeler, Research Dietitian at UCL Great Ormond Street Institute of Child Health, commented: “This novel dietary approach for epilepsy management involves following the principles of a healthy balanced diet alongside use of K.Vita, allowing greater dietary freedom compared to ketogenic diets. Our approach also requires much less input from a specialist dietician than is required by traditional ketogenic diets, and so may allow more widespread access to people with drug-resistant epilepsy.”

Researchers say larger, controlled studies of K.Vita are now needed to determine the precise epilepsies and conditions in which the supplement is most effective.

Patients were recruited from Great Ormond Street Hospital, Chalfont Centre for Epilepsy and The National Hospital for Neurology and Neurosurgery, part of UCLH.

*From the article here :
 
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Psilocybin and Epilepsy

by Haley Ritter

I'm currently 41 years old, and I've lived with epilepsy literally my whole life, since my mom first noticed my uncontrollable giggling as a 2-year-old (Gelastic/Simple Partial seizures-SPs). My pediatrician at the time (1979) dismissed these episodes as "anxiety attacks" (my mom rolled her eyes and simply continued to watch carefully whenever I had these giggle spells as I progressed through elementary school). Then, as my hormones kicked in during adolescence (age 11 or 12) my seizures matured into Complex Partials (CPs) and I was finally diagnosed with Epilepsy. We still had neurologists that claimed I was making them up to get attention because all my EEGs were "normal" (this was back ~1989/'90 and technology was barely starting: i.e. CT/CAT scans, MRIs came a little later, and those tests were all "normal" too).

Meanwhile, new anti-convulsants were coming out like crazy at the time, and I was being tested like a guinea pig: one med after another proved to have zero control on my weekly, and daily, seizures (CPs and SPs, respectively). They kept getting worse, more frequent, and became Myoclonic in High School, despite all the meds they were feeding me like candy, and one that almost killed me my senior year (Felbamate/Felbatol) due to severe depression and thoughts of suicide.

I started college in Fall of 1995, and my H.S. sweetheart and I were still together, but had a nice, solid, long-distance relationship during which we saw each other 2-3x/year, and did regular magic mushroom trips together. I quit having seizures COMPLETELY for 2 ENTIRE YEARS during that period of my life and even got my drivers' license when I was 20 years old!!! <---(That was something I never learned how to do when I was 15-16 years old because I had so many seizures and it wasn't a safe or legal option for me).

After we broke up in '98, mushrooms were not an option for me anymore and sure enough, I started having seizures again! Those progressed into Tonic Clonics (TCs or "Grand Mals") very quickly, and in the Fall of 2003 I started having 3-5 of those PER DAY! I was just beginning my career as an ASL Interpreter for the Deaf/Hard-of-Hearing and had my first job, but couldn't handle working full time at a Middle School, interpreting for a hyperactive, aggressive 14 year-old Deaf kid who couldn't control himself, and freaked out every time I dropped on the floor convulsing like crazy 2-3 times a day. I was 26 years old, and finally went ahead with my neurologist's suggestion to have a Right Temporal Lobectomy because I was desperate. I was still having TCs SPs like crazy. Then I had another brain surgery in 2012 when technology was improved and they finally found a "cause" for my seizure activity.

As it turns out, I have a very rare brain tumor on the right side of my hypothalamus: "Hypothalamic Hamartoma (HH)" that I was born with, so my seizures were coming from this benign bundle of abnormal nerve tissue that behaves like a pacemaker would act on the heart- constantly stimulating that vital area of my brain with electrical impulses that spread into seizures. During this 4th (and FINAL, mind you) surgery, they radiated my tumor with "Gamma Knife" technology by drilling a huge metal frame onto my skull and sticking my head in a tube for 4 hours. Nothing changed, I still have 5-15 SPs everyday, 2-3 TCs per month, and now they want to do yet ANOTHER brain surgery on me (HECK NO!!! I'm DONE). About a year ago, I began experimenting with daily micro-doses of mushrooms, and finally have had 2 months where I've been completely seizure-FREE!! This has been the ONLY successful treatment for my seizures!

https://www.epilepsy.com/connect/forums/epilepsy-and-college/shrooms-and-epilepsy
 
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CBGA more effective for seizures than CBD, study
by Benjamin Adams | High Times | 5 Oct 2021

Researchers in Australia say they’ve discovered the “mother of all cannabinoids,” and it isn’t THC or CBD. For the first time, a study reports that three acidic cannabinoids found in cannabis, notably cannabigerolic acid (CBGA), reduced seizures in a mouse model of Dravet syndrome, an intractable form of child epilepsy.

The three acidic cannabinoids—CBGA, cannabidivarinic acid (CBDVA) and cannabigerovarinic acid (CBGVA)—”may contribute to the effects of cannabis-based products in childhood epilepsy,” and were noted with “anticonvulsant potential.” CBGA, however, demonstrated the most potential for certain anticonvulsant effects.

“From the early nineteenth century cannabis extracts were used in Western medicine to treat seizures but cannabis prohibition got in the way of advancing the science,” said Associate Professor Jonathon Arnold from the Lambert Initiative for Cannabinoid Therapeutics and the Sydney Pharmacy School. “Now we are able to explore how the compounds in this plant can be adapted for modern therapeutic treatments.” The study was recently published in the British Journal of Pharmacology.

CBGA is the precursor “granddaddy” molecule of CBDA and THCA, which eventually convert to THC and CBD, among other compounds. CBGA is part of a protective system for cannabis, produced by trichomes that triggers targeted plant cell necrosis—natural self-pruning to allow the plant to focus energy on the flower.

“We found that CBGA was more potent than CBD in reducing seizures triggered by a febrile event in a mouse model of Dravet syndrome,” Lead author of the study, Dr Lyndsey Anderson, said. “Although higher doses of CBGA also had proconvulsant effects on other seizure types highlighting a limitation of this cannabis constituent. We also found CBGA to affect many epilepsy-relevant drug targets.”

Fight against Dravet Syndrome with CBGA

The mission for the team at the Lambert Initiative for Cannabinoid Therapeutics is simple: develop a better cannabis-based treatment for Dravet syndrome—an intractable form of child epilepsy.

In 2015, Barry and Joy Lambert made a hefty donation to the University of Sydney to push forward scientific research on medicinal cannabis. Barry and Joy’s granddaughter Katelyn suffers from Dravet syndrome.

“After using hemp oil for treatment, we got our daughter back. Instead of fearing constant seizures we had some hope that our daughter could have a life worth living. It was like the noise cleared from her mind and she was able to wake up. Today Katelyn really enjoys her life,” said Michael Lambert, Katelyn’s father.

In order to learn more, the research needs to be continual. “Our research program is systematically testing whether the various constituents of cannabis reduce seizures in a mouse model of Dravet syndrome,” said Associate Professor Jonathan Arnold. “We started by testing the compounds individually and found several cannabis constituents with anticonvulsant effects. In this latest paper we describe the anticonvulsant effects of three rarer cannabinoids, all of which are cannabinoid acids.”

The Entourage Effect

In the meantime, anecdotal evidence from cannabis consumers abroad suggests that there is more to cannabis’ healing powers than THC and CBD, although the science is limited.

Families like the Lamberts have noticed significant drops in seizures when children facing intractable epilepsy take cannabis extracts, although the source makes huge differences.

Supporting the concept of the Entourage Effect, there are unknown benefits from lesser known cannabinoids. Many people believe that the presence of terpenes and other compounds in cannabis make it more effective.

Harvard Professor, Dr. Lester Grinspoon, said that "you need more than THC and CBD if you want cannabis’ full effects. It should be called the Ensemble Effect, not the Entourage Effect," he said. Dr. Grinspoon believed THC should be taken with CBD and other phytochemicals in order to be more effective. Any chemical in isolation does not perform the same way as it is found in nature, he believed.

Dr. Raphael Mechoulam is best known for his extensive work in cannabis acids, as well as Dr. Ethan Russo. In 1996, Japanese researchers found that CBGA is a precursor to CBDA and other compounds.

*From the article here :
 
There are recent studies that have shown great resuslt's of Bumetadine for Autisme. By way of targeting the root of the problem. That seem's to be having its origin in dis-regulated sensory processing. Bumetadine showed great improvement in 10 to 20% of the test group. vs 0% in the placebo group.

The theory: the body can't get rit of Chloride that infants apparently have in their brains. Normally it is removed but something goes wrong when they age, the Chloor stay's there and causes disruptions in normal brain function. Causing an overload of sensory input. This treatment could also be used for ADHD and Epilepsy.

The difference the patient they showed was remarkable. From not being able to eat diner with his family to actually enjoying it.

Found the link to the publication in 'Biological Psychiatry'
https://www.biologicalpsychiatrycnni.org/article/S2451-9022(21)00251-2/fulltext

This i found on Pubmed kinda related. But an other trial, so in 2013 they were already looking in that direction.
https://pubmed.ncbi.nlm.nih.gov/23061490/
 
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Ending the pain of children with Severe Epilepsy? The impact of Medical Cannabis*

Zafar R, Schlag A, Nutt D. Drug Science, Policy and Law. January 2020.

This study assessed the impact of whole-plant medical cannabis oils including THC and CBD in 10 children with a diagnoses of severe treatment resistant epilepsy.

All children had previously failed on anti-epileptic drugs and other supportive therapies including vagal nerve stimulation, ketogenic diet and the licensed CBMP Epidiolex. All children in our study managed to show an improvement in monthly seizure frequency when using whole-plant medical cannabis. Seizures fell by 80% across the group of children after starting treatment, with two children achieving complete seizure freedom.

The use of anti-epileptic drugs, known to have deleterious effects on development and cognition, were reduced from an average of 8 AEDs to 1 AED per patient following treatment with medical cannabis.

We found that parents were paying around £1800 per month to obtain these private prescriptions from specialists’ clinics due to the refusal of the NHS and the CCGs to pay for them. The refusal by the NHS and CCGs to prescribe is based on pressure from the BPNA and NICE who refuse to acknowledge the positive clinical impact these drugs are having in completely reversing their conditions, despite us finding such clinically impactful results.​

Monthly Seizure Frequency Pre & Post Initiation of Cannabis Based Medicinal Products
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For open-access to the full report of this research, click here.

*From the article here :
 
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Medical Cannabis and Epilepsy in the UK – A Qualitative Analysis of the Carers’ Perspective

by Schlag A, Zafar R and Nutt D. | Drug Science, Policy and Law | 21 Jan 2021

Following on from our quantitative study highlighting the effectiveness of CBMPs to treat severe intractable childhood-onset epilepsy, for the present study, we used a narrative, open-ended approach to interview 11 parents/carers of these patients. We aimed to understand the families’ situation in more depth, and to contextualise our previous findings.

It was heart-breaking to see that, although these families have found CBMPs to be the most effective treatment for their child’s condition, unfortunately access to these medicines remains severely restricted, causing serious challenges in their day-to-day life.

Looking at the wider picture, parents/carers highlighted the broad range of issues they experienced in relation to medical cannabis – these included the challenging regulation and policy surrounding medical cannabis, their anger and sheer desperation related to these policies, as well as the broad variety of benefits experienced as a result of using the medicine.

Evidently, the benefits of medical cannabis for these children far outweigh any associated risks (please see Fig 1). All families agreed that CBMPs allow their children a substantially better quality of life than is possible on other AEDs alone.

Many of the issues raised in our study are not about the science of medical cannabis per se. Rather, they are political issues, related to the wider issue of trust and power in society, and the importance of expert versus lay opinions. This has wider implications than medical cannabis alone.

The way that families are treated contrasts markedly with the way they would like to be treated and emphasises the importance of including patients in decision-making about their medical plans and the value that should be given to their reported outcomes and wishes. A holistic model of care – with more focus on compassionate and ethical treatment of patients and their families – is essential. Access to CBMPs is one important aspect of this, together with more professional support, better communication with clinicians and policy makers who need to do more than pay lip service.​

Perceived benefits vs risks of medical cannabis

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Read the full paper

 
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Drug Science's Recommendations:
Medical Cannabis in Relation to Children with Treatment-Resistant Epilepsy


Most of the families in our studies still require affordable and sustainable access to their CBMPs. It remains a matter of urgency to improve access to medical cannabis for these children. We outline the following recommendations to improve patient access – some of these are specific to paediatric epilepsy but most carry general relevance.​

Mandate the NHS to fully fund the treatment costs for current patients once their consultant has agreed that there is adequate clinical benefit
  • As the UK is now left with only one prescribing neurologist privately, further physicians need to be educated and trained urgently (e.g., through Medical Cannabis Clinician’s Society)
  • Remove the need for BPNA involvement in these
  • Provide training for other specialists and GPs who would like to learn how to prescribe
  • Support and encourage GPs to take shared care for these children and so be allowed to continue prescribing under the specialist supervision
  • Collect nationwide data on these and other similar children using a data base such as for the Drug Science’s Project Twenty21 initiative
  • Use this data base to evaluate effectiveness of medical cannabis in these children using real world data
General Recommendations for Medical Cannabis
  • Involve patients in their care and listen to parents/carers
  • Make a wider range of CBMPs available on the NHS - especially for patients who have been shown to benefit f rom the medicine
  • Reduce stigma towards and ignorance of medical cannabis by supporting education for doctors and healthcare professionals
  • Widen the NICE evidence base to include real world data to complement RCTs
  • Conduct a full health economics analysis of the value of medical cannabis in some syndromes where clinical trials are unlikely to be conducted
  • Build up the current evidence base by providing research funding
  • Establish an Office of Medical Cannabis (as e.g., in the Netherlands) to address issues efficiently
  • Reschedule d9THC to Schedule 2 to facilitate research

Drug Science's Response to UK Government Recommendations for Medical Cannabis

 
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Ketamine could treat this rare form of Epilepsy*

Psychedelic biotechnology company PharmaTher is also exploring if ketamine can treat other neurological conditions, including Parkinson’s Disease, ALS, and CRPS.

by Emily Jarvie | PSYCHEDELIC SPOTLIGHT | 24 Nov 2021
Psychedelic biotechnology company PharmaTher believes ketamine could treat yet another rare neurological condition — Status Epilepticus (SE).

The company has applied to the United States Food and Drug Administration (FDA) to receive orphan drug designation for ketamine to treat this condition.

Orphan drug designation is granted to drugs or biological products that show the potential to treat a rare disease, defined by the FDA as conditions that affect fewer than 200,000 people in the United States at any given time. This status provides various benefits and incentives to companies — such as market exclusivity, possible tax credits, and the waiver of the FDA New Drug Application filing fee, which usually costs about $2.4 million — to encourage the development of products to treat these rare diseases.

PharmaTher has already successfully achieved orphan drug designation for ketamine to treat amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, and complex regional pain syndrome (CRPS).

SE is a life-threatening condition where a person experiences a prolonged seizure, lasting more than five minutes or recurrent seizures (more than one within five minutes) where a person does not recover consciousness in between them. Usually, seizures do not last longer than two minutes. Most people with epilepsy have short seizures that stop by themselves, but sometimes the episode can last too long and become SE, requiring emergency treatment.

This condition is considered a medical emergency that could lead to permanent brain damage or death if not treated immediately. Sadly, the mortality associated with SE varies from 5% to 50%, depending on the study. In elderly patients, refractory SE (meaning the patient is resistant to first-line medications) causes death in more than 76% of cases.

SE can occur with any type of seizure, not just in people who have been diagnosed with epilepsy, and it can happen to people who have never had a seizure before. In adults, common causes are a stroke, head injury, or drug or alcohol abuse. Although there is a lack of epidemiological evidence about SE, it was projected in 2020 that the incidence of the condition in the United States, across all age groups, is anywhere between 18.3 to 41 people per 100,000 per year.

Early treatment of the condition involves benzodiazepines — a class of psychoactive drugs that lower brain activity, often prescribed to treat seizures, anxiety, and insomnia. However, about a third of patients with SE are refractory and continue to have episodes, requiring aggressive management of their condition with other medications.

However, PharmaTher believes ketamine can potentially treat various mental health conditions and pain and neurological disorders, including SE. “We are focused on expanding ketamine’s therapeutic utility in rare disorders and life-threatening conditions, including, but not limited to, Parkinson’s Disease, ALS, CRPS, and now SE,” explained PharmaTher CEO Fabio Chianelli.

“The FDA orphan drug application for ketamine to treat SE builds on our belief in the potential of ketamine to improve quality of life and to save lives.”

*From the article here :
 
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CBGA, CBDVA, CBDV and CBGVA reduce seizures in a mouse model of intractable epilepsy.


Cannabinoid salts found to reduce seizure activity*

University of Sydney | Neuroscience News | 5 Oct 2021

Summary: Scientists have identified three acidic cannabinoids in cannabis that reduces seizure activity in mouse models of Dravet syndrome.

Research from pharmacologists at the University of Sydney provides new insights into how cannabis extracts may work to treat epilepsy.

The study for the first time reports that three acidic cannabinoids found in cannabis reduced seizures in a mouse model of Dravet syndrome, an intractable form of childhood epilepsy.

The study has been published in the British Journal of Pharmacology.

“From the early nineteenth century cannabis extracts were used in Western medicine to treat seizures but cannabis prohibition got in the way of advancing the science,” said Associate Professor Jonathon Arnold from the Lambert Initiative for Cannabinoid Therapeutics and the Sydney Pharmacy School.

“Now we are able to explore how the compounds in this plant can be adapted for modern therapeutic treatments.”

In 2015, Barry and Joy Lambert made a historic donation to the University of Sydney to advance scientific research on medicinal cannabis and cannabinoid therapeutics. Barry and Joy’s granddaughter Katelyn suffers from Dravet syndrome, which features frequent seizures and causes delays in cognitive and motor development. Conventional therapies often do not provide adequate seizure control and patients have a reduced quality of life.

The Lambert family say they witnessed a dramatic improvement in Katelyn’s health using a cannabis extract and became ardent supporters of cannabis for therapeutic treatment. They also wished to better understand how cannabis works to treat epilepsy and other health conditions.

“After using hemp oil for treatment, we got our daughter back. Instead of fearing constant seizures we had some hope that our daughter could have a life worth living. It was like the noise cleared from her mind and she was able to wake up. Today Katelyn really enjoys her life,” said Michael Lambert, Katelyn’s father.

In 2015 the Lambert Initiative established a preclinical epilepsy research program to help understand how cannabis extracts, a mixture of hundreds of bioactive molecules, have anticonvulsant effects.

Associate Professor Arnold said: “Our research program is systematically testing whether the various constituents of cannabis reduce seizures in a mouse model of Dravet syndrome. We started by testing the compounds individually and found several cannabis constituents with anticonvulsant effects.”

“In this latest paper we describe the anticonvulsant effects of three rarer cannabinoids, all of which are cannabinoid acids.”


Acidic cannabinoids are the cannabinoids that are biosynthesised in the plant and are found in artisanal cannabis extracts used to treat children with epilepsy. One of these cannabinoids, cannabigerolic acid (CBGA), is the “mother of all cannabinoids”, Associate Professor Arnold said, as it is the precursor molecule to the creation of better-known cannabinoids, like cannabidiol (CBD) and tetrahydrocannabinol (THC).

“The cannabinoid acids are abundant in cannabis but have received much less scientific attention. We are just beginning to understand their therapeutic potential,” Associate Professor Arnold said.

Lead author of the study, Dr Lyndsey Anderson, said: “We found that CBGA was more potent than CBD in reducing seizures triggered by a febrile event in a mouse model of Dravet syndrome. Although higher doses of CBGA also had proconvulsant effects on other seizure types highlighting a limitation of this cannabis constituent. We also found CBGA to affect many epilepsy-relevant drug targets.”

The study involved University of Sydney researchers in the School of Psychology and the Sydney Pharmacy School in collaboration with the laboratory of Dr Jennifer Kearney at Northwestern University (US). Dr Kearney developed the genetic mouse model used in the study and mentored Dr Anderson before she moved to Australia.

The team is continuing their research hoping to develop a better cannabis-based treatment for Dravet syndrome. Many in the community strongly believe there is something uniquely therapeutic about the full spectrum of cannabis components working together.

“We have assessed the cannabinoids one by one and now we are exploring what happens when you put them all back together. There remains a real possibility that all these individual anticonvulsant cannabinoids might work better when combined,” Dr Anderson said.

Barry Lambert said: “We are very proud of the work done by the many researchers at the Lambert Initiative, which is a world-leader in cannabinoid research, and in particular welcome these recent results on ‘the mother of all cannabinoids’.”

*From the article here :
 
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Psychedelics and Epilepsy | My Story

by seamuspg | Epilepsy Foundation

I put my story here mostly to serve as a reference should anyone be inquiring about the use of Psychedelics and Epilepsy. It's a rather simple story, but I believe it's one that could be extremely informative to some people.

I was a healthy 39-year-old male who battled a low lying depression for much of my adult life. After not responding to countless hours of talk therapy, and numerous SSRi's I became interested in utilizing Psychedelics as a mode for therapy. For those who aren't aware, we are currently in what is being described as the "2nd Renaissance" of Psychedelics. They are showing great potential and efficacy in treating various conditions where current medications and treatments are proving ineffective. For example, MDMA (ecstacy) will be FDA approved for PTSD by the end of 2021, Psilocybin (magic mushrooms) are expected to be approved for anxiety, alcoholism, etc by 2023. Other substances such as Ayahuasca and Ibogaine could be close behind.

I only give the backstory because it makes clear my intentions. I had no desire for recreational use. I wanted to feel better, to get to the root of my problems, rather than simply numb the symptoms with more medications.

I was 39 years old,.I had never had a single epileptic "episode" of any kind. I'm not sure I knew what the word meant. I decided to participate in 4 Ayahuasca ceremonies (Peru) under the guidance of a well respected Shaman. I n short had a variety of experiences, but one, in particular, was earth-shattering to my psyche. When I came back to "earth" I knew full well that this experience was not over, and I would be greatly impacted as began the road to "recovery" and "re-integration". I just didn't know how or to what extent.

Two days after that hell-ish experience, I was on a plane flying home back to Boston, when I experienced my first "what the hell is going on moment". I started having a confusing "deja-vu, dreamlike, familiarity / dual consciousness", experience that came with anxiety and confusion. I remember looking at a text that I had written moments before and I had 0 recollection of having written anything of the sort. I swore I hadn't written it. As one can imagine, this only increased the anxiety.

These occurrences started happening much more frequently to the point where I had multiple episodes in a day. I was so "destabilized" from the Ayahuasca experience, I was having a hard time differentiating what was what. I was battling a darkness and a fear beyond belief but also experienced these deja vu episodes that left me confused and with impaired cognition and memory. I eventually understood that they were separate from the "darkness" and after doing some research, I realized my descriptions were those shared by many who suffer from temporal lobe epilepsy. I eventually saw a neurologist, had several EEG's and the diagnosis was confirmed... Temporal Lobe Epilepsy stemming from the left temporal lobe. My neurologist (well renowned, Boston) had no prior experience with Psychedelics being the catalyst for Seizures. In fact he wanted to document my case. I am currently on Lamictal which has greatly diminished the episodes.

I share this story merely as a reference. I actually still believe in the potential of Psychedelics for therapy due in part to their ineffable power. But the same power that can re-wire brains, change chemistry, and allow for new behaviors and patterns to emerge, can also have long-lasting effects that are not so welcomed. I just think it's worth knowing this story for anyone who is educating themselves on the pros/cons of utilizing thee substances as therapy. Whether my current condition was caused the "DMT molecule" or the traumatic "experience" I will never know. Maybe both.

(Many people will say "you must have been pre-disposed" to the condition and the Psychedelics brought it to the surface. Goodness, that argument is so silly. For one, it isn't "prove-able", nor has it ever been or ever will be. Secondly, that's like saying someone who smokes and develops cancer was pre-disposed to the disease. It doesn't hold weight, and it actually doesn't matter since no one knows what their "predisposition" is. I have no immediate family members or relatives with Epilepsy.)

 
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Imperial College London

Cannabis cuts seizures by 86 percent in epileptic children

by Rich Haridy | New Atlas | 14 Dec 2021

A small UK study has found epileptic children treated with whole plant medicinal cannabis products displayed an 86 percent average reduction in seizure frequency. The researchers behind this series of case reports call for direct clinical trials to test whether whole plant cannabis oils are more effective at treating epilepsy than products solely containing cannabidiol (CBD).

In 2018 a CBD formulation called Epidiolex was approved by the US Food and Drug Administration (FDA) to treat severe forms of childhood-onset epilepsy. It was the first cannabis-derived medicine to be approved for any medical use in the United States.

For well over a century scientists have recognized cannabis to be an effective anticonvulsant, and more recent research has suggested CBD to be primarily responsible for those therapeutic benefits. But Epidiolex, and other CBD-focused products, haven’t always been effective in everyone and some researchers have speculated the therapeutic outcomes of cannabis to be influenced by the synergistic effect of hundreds of different distinctive compounds found in the plant.

This new research, published in the journal BMJ Pediatrics Open, reports on 10 case studies of children using whole plant cannabis extracts to treat severe epilepsy. Overall, the study found the children reported an 86 percent drop in seizure frequency using a variety of whole plant products.

It is important to note these findings are observational and retrospective. This study was not a controlled trial with a placebo group but instead it covers 10 separate case studies, all of which have unique case histories.

Two of the children in the study, for example, previously tried Epidiolex to control their seizures with no success. And a number of different whole plant cannabis extracts were utilized by the children in the study, all with varying CBD and THC concentrations.

The researchers also note there is little data on the chemical makeup of these whole plant products beyond THC and CBD concentrations. So it is unclear exactly what combination of other cannabis compounds could be playing a role in the therapeutic outcomes.

It is only recently that researchers have begun to investigate the myriad of unique chemicals in cannabis, from lesser known cannabinoids such as CBGA, to a unique class of compounds known as terpenes. The new study calls for more research into the therapeutic effects of these little known compounds.

The study also addresses the controversial topic of administering THC to children in a therapeutic context. The researchers note any potential deleterious effects in children from whole plant cannabis products must be weighed against the known adverse effects from many anti-epileptic drugs (AEDs).

“… adverse effects from AEDs are the leading cause of treatment discontinuation and after seizure frequency, the major determinant of impaired health-related quality of life in people suffering with epilepsy,” the researchers write. “Adverse events are commonly reported with AEDs with one such study reporting 1139 adverse drug reactions in 124 young people using anti-epileptic drugs while another study reported that behavioural problems and somnolence were the most common adverse drug reactions and that AED polytherapy significantly increase the likelihood of children developing such reactions.”

Jonathon Arnold, a cannabinoid researcher from the University of Sydney, says these new findings are promising. He notes his preclinical research has identified several molecules in cannabis with anticonvulsant properties and a clinical trial to explore whole plant cannabis products in intractable childhood epilepsy patients is certainly warranted.

“It may be that whole plant cannabis is effective in not only reducing seizures but assisting in behavioral and cognitive impairments,” says Arnold, who did not work on this new study. “That medicinal cannabis reduced the number of conventional anti-seizure medications used is promising but more data is needed."

The new study was published in the journal BMJ Pediatrics Open.

Source: BMJ

 
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CBD stops epileptic seizures*

by David Kohn

Jackson Leyden had always been a healthy kid; he practiced taekwondo, and he played lacrosse and baseball. But in 2011, a few months after his eighth birthday, he began having seizures several times a day. Many were brief, a half-minute of staring into space, but he also had severe episodes in which he would collapse, sometimes injuring himself. Over the next two years, he was hospitalized about 50 times, and he missed much of fourth and fifth grade.

His parents took him to more than 20 doctors around the country, and he tried more than a dozen medications. Nothing worked. Two years ago, the Leydens were at the end of their rope. They decided to see whether marijuana might help. (Medical use of the drug is legal in the District, where they live, and the Leydens found a doctor willing to work with them.) In 2014, Jackson got his first dose of cannabis.

“Within a few days, he was having hardly any seizures,” says his mother, Lisa. “I was shocked.” Over the next few months, he stopped taking other medications.

Not only did the medicine help, it did so without making him high. The strain of marijuana that Jackson takes is unusual: It contains high levels of cannabidiol, or CBD, one of the two main molecules in marijuana; the other is tetrahydrocannabinol, or THC. While THC is famously mind-altering, CBD is not.

Over decades, researchers have found that THC may help treat pain, nausea, loss of appetite and other problems, while CBD was thought to be biologically inactive in humans. But in the past 10 years, scientists have concluded that CBD may be quite useful. Dozens of studies have found evidence that the compound can treat epilepsy as well as a range of other illnesses, including anxiety, schizophrenia, heart disease and cancer.

Now 13, Jackson — whose diagnosis is undetermined — continues to use marijuana every day. (Like many patients, he ingests it in droplet form, which allows for more precise dosing and avoids lung problems.) He still has seizures, but they are less severe and they occur once every week or two, down from around 200 a month before he started using cannabis. He is back in school full time and is well enough to go on hikes and bike rides with his family.

Thousands of people around the country are using high-CBD marijuana.

“This is a really powerful compound,” says Mikhail Kogan, the medical director of the George Washington University Center for Integrative Medicine. “I’ve seen it work for a lot of my patients.” He prescribes high-CBD strains of cannabis regularly for such illnesses as epilepsy, post-traumatic stress disorder, anxiety, autoimmune disorders, autism and insomnia.

‘A game-changer’

In the cannabis plant, CBD and THC generally have an inverse relationship: The more THC there is, the less CBD, and vice versa. In recent years, growers have bred some plants to contain high levels of CBD. Some say the two compounds work synergistically and that for many ailments, combining CBD and THC is best.

What makes CBD especially appealing is that it doesn’t get the user high. Most recreational marijuana users want this effect, of course, but many patients would rather avoid it. This has allowed CBD to sidestep many of the political, legal and medical concerns that have hindered the spread of medical marijuana.

“CBD has been a game-changer for medical marijuana,” says Martin Lee, the director of Project CBD, a Northern California nonprofit that promotes use of the compound. “Its safety and lack of psychoactivity undermines any argument that it should be illegal. It’s really shifted the national discussion on this issue.”

As more scientists recognize the compound’s potential, there has been an “explosion of research,” according to Pal Pacher, a pharmacologist and cardiologist at the National Institutes of Health in Bethesda. He has been studying the chemical for more than a decade; his work has shown that CBD may have benefits in both heart disease and diabetes.

One key area of CBD research is epilepsy. Several scientists are focusing on its potential to reduce seizures, especially among those for whom other treatments have failed. “We’ve found significant positive effects with CBD,” says New York University neurologist Orrin Devinsky, who studies the compound for severe childhood epilepsy.

In a study whose findings have not yet been published, he and a colleague, Daniel Friedman, found that patients receiving CBD in addition to their usual medicines had 39 percent fewer convulsive seizures than patients who remained on their normal drug regimen. "Given that the study included only the most treatment-resistant patients, this is an 'excellent response,'” Devinsky says.

Much more research is needed, he says, to establish whether CBD works, and if so for what conditions, but he understands that severely ill patients, or their parents, may not want to wait for this data: “If other drugs don’t work, it’s certainly reasonable to try this.”

The compound has also shown promise in treating anxiety, depression and schizophrenia. Much of this work has been in rats and mice, but several studies have found benefits for humans. For instance, German researchers showed in 2012 that giving CBD to schizophrenic patients reduced psychotic symptoms such as hallucinations and disordered thinking.

CBD seems to have anti-cancer properties, too. At the California Pacific Medical Center Research Institute in San Francisco, researchers Sean McAllister and Pierre Desprez have found that CBD can block cancer cells from metastasizing.

It’s not clear how CBD works. This is partly because it stimulates multiple biochemical pathways, which may account for its wide range of effects. The compound is a powerful anti-inflammatory and antioxidant, and it increases levels of the neurotransmitter serotonin as well as another molecule, anandamide, which reduces pain and anxiety.

Francisco Guimaraes, a pharmacologist at the University of Sao Paolo in Brazil, has found that it increases growth of new neurons in the brain, especially in the hippocampus, a region that plays a key role in depression and anxiety.

“CBD is a Disneyland for a pharmacologist,” he says. “There are so many possible mechanisms, so many possible ways it can be useful.”

But studying CBD is not easy: Scientists complain that laws and regulations put excessive constraints on their work. Although it doesn’t make users high, CBD (both the molecule and CBD-rich cannabis) is classified by the federal government as a Schedule 1 drug, which means they have high potential for abuse and no accepted medical use.

The list includes marijuana (undifferentiated by strain) and heroin. (While the federal government oversees marijuana research, marijuana use is regulated, in part, by state laws.) As a result, scientists who study the compound must follow a host of restrictive rules. Last year, responding to a request from several governors to change marijuana’s designation, the Drug Enforcement Administration announced that all cannabis would remain a Schedule 1 drug.

Still on Schedule 1

“It’s ludicrous and arbitrary,” according to Devinsky, who says getting government approval for his epilepsy trial required dozens of hours of extra work. Like most scientists who study the compound, he uses almost pure CBD. Although not at all psychoactive, it must be kept in a heavy safe with an alarm system.

Even as the research proceeds, thousands of people are using CBD as medicine. A British pharmaceutical company, GW Pharma, has developed two CBD drugs: Sativex, which contains a 1-to-1 ratio of CBD and THC, and Epidiolex, which is pure CBD. The former is prescribed for the painful muscle spasms that occur in multiple sclerosis, while the latter is aimed at childhood seizures. Sativex is not available in the United States, but it is approved in 29 other countries, including Canada, England and Israel.

Epidiolex has not been cleared for sale anywhere in the world; GW Pharma says it expects to begin the approval process with the Food and Drug Administration next year.

And thousands of Americans are using strains of cannabis with a strong CBD content. Advocates and medical marijuana dispensaries agree that as awareness about CBD grows, so does demand.

Stephanie Kahn, who with her husband, Jeffrey, runs the Takoma Wellness Center, a medical marijuana dispensary in Northwest Washington, says that about half of her 1,200 patients use CBD-rich products. Her dispensary offers several strains of high-CBD cannabis as well as CBD oil, with different ratios of CBD and THC, each of which she recommends for particular conditions. “We get questions about it every day,” she says. “A lot of our patients get relief with this, and a lot of times this works better than pharmaceutical drugs.”

No insurance

The cost of treatment varies: Depending on the dispensary and the dosage, it can range from around $100 a month to more than $1,000. Despite the cost, which is not covered by insurance, CBD medicines are drawing great interest for children with severe, intractable epilepsy. California and Colorado, which were among the first states to legalize medical marijuana, have become hot spots for such patients. Before other states legalized medicinal CBD use, some families moved to these states so they could have access to the compound.

One of the most experienced practitioners in this field is Los Angeles physician Bonni Goldstein, who has used the compound to treat dozens of children with intractable epilepsy. She says about half of these patients have seen a significant drop in the number of seizures. “Used in the right way, with the right patient, CBD is extremely powerful,” she says.

Yet even those who believe in this power recognize that CBD medicine remains largely unexplored: Treatments are not systematized, many products are not standardized or tested, and patients (or their parents) are generally left to figure out dosing on their own. While some suppliers and dispensaries test the CBD and THC levels of their products, many do not. “We really need more research, and more evidence,” Kogan says. “This has to be done scientifically.”

For Lisa Leyden, Jackson’s mother, these issues don’t negate the compound’s enormous potential. “I realize this isn’t perfect,” she says. “We absolutely need to know more. But in the meantime, many people need help. They’re in bad shape, and this seems to work.”

*From the article here :
https://www.washingtonpost.com/nati...ory.html?noredirect=on&utm_term=.fa313f204427
 
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Yale School of Medicine

The effects of Ketamine in individuals with Epilepsy, study

by Elizabeth Watson | YALE | 7 Jun 2022

A Yale researcher has received a grant from the Yale Swebilius Pilot Research Program in Epilepsy to study the effects of ketamine in individuals with epilepsy.

Sarah Fineberg, an assistant professor of psychiatry at the Yale School of Medicine and an attending psychiatrist at the Connecticut Mental Health Center, will be the principal investigator of a study investigating the impact of ketamine, a short-acting anesthetic, on individuals suffering from epilepsy. Collaborators on the study include Eyiyemisi Damisah, assistant professor of neurosurgery and neuroscience; Alfred Kaye, assistant professor of psychiatry; and John Krystal, professor and chair of the department of psychiatry.

“I love doing work at the intersection of patient experience and neurobiology,” Fineberg said. “This project directly relates experiences that patients can feel and describe to basic elements of neural function.”

It was in the mid-90s when Krystal, alongside his colleagues, was able to identify that the drug ketamine had the potential to exhibit antidepressant effects. Now, Fineberg hopes to further evaluate ketamine’s antidepressant effects by studying them in relation to individuals with a history of seizures. Since arriving at Yale in 2010 after completing a MD-PhD program at the University of Iowa, Fineberg has focused on clinical research in the context of studying mood symptoms, particularly in groups that have been historically excluded from psychiatric studies, such as individuals with epilepsy.

Studying the neural mechanisms of such disorders as they occur in the brain can be difficult due to the skull acting as a barrier, according to Krystal. To overcome this obstacle, non-invasive neuroimaging techniques, such as EEG or MRI, are used to study brain activity. Still, direct electrical recording of brain activity remains essential. In the case of Fineberg’s study, the team plans to seek out individuals who have previously been treated with chronic intracranial electrodes to help manage their seizures. In doing so, the researchers hope to utilize the intracranial electrodes to measure the participants’ neural signals after taking ketamine to determine how they relate to the emotional states of the participants, as well as how their seizures are responding to the drug.

“I am thrilled to work with Drs. Fineberg and Damisah and their team in a study that will, for the first time, record directly from human brain circuits as they are exposed to ketamine and relate the ketamine effects to improvements in depression,” Krystal said. “This could shed light on the underlying biology and potentially provide new biomarkers of depression and its treatment.”

Using these chronic intracranial electrodes could provide crucial insights into the effects that occur after ketamine dosing. Dissociation, or the state of feeling disconnected from the passage of time or one’s own body or thoughts, is a common side effect of taking ketamine. Monitoring the neural signals of the participants in the one to two hour window that dissociation generally takes place in could be essential to deriving its neural basis and in turn, developing a better understanding of both ketamine and depression in the context of epilepsy.

“Recognition of knowledge of the nonmotor manifestations of epilepsy holds inherent value for the well-being of these patients,” said Shanae Aerts GRD ’26, a graduate student in the interdepartmental neuroscience program at Yale’s Blumenfeld lab — which studies the relationship between consciousness and epilepsy. “By nature, symptoms like depression are more difficult to see yet can have a large impact on quality of life.”

The initial research into the antidepressant effects of ketamine in the 1990s helped lay the groundwork for the development of the antidepressant Esketamine, commonly known as Spravato, by Janssen Pharmaceuticals.

*From the article here :
 
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