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    #26
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    To anyone with social anxiety looking to self medicate with psychedelics

    This is an ongoing series of posts I'm creating in order to help those suffering with severe social anxiety looking to self medicate in a safe, healthy, and effective manner.

    Psychedelics can be a very valuable tool in your arsenal, and they're used in a wide variety of different ways. From the adventurous party goer dropping acid at a rave, to the philosophical monk taking a trip to South America for an Ayahuasca, these are some of the most diverse substances known to mankind. I've personally employed the usage of them for both recreation, and soul searching, and there's something I need to stress. Psychedelic drugs are not the be all end all wondrous source of enlightenment that many die hards would have you believe. Some of the "epiphany's" one can reach have no basis in reality at all. Also, in the vast majority of cases you're not going to have a great/bad trip and suddenly be cured of your social anxiety. Going into my first few experiences I had read anecdotal stories of such things happening, and wanted nothing more, having a mind set like mine will likely ensure that you don't. With that being said, these drugs can help you realize things pertaining to yourself/the world which you may not have normally been able to while sober. The following story is about just that....

    Allow me to take you back to my senior year of high school. I was depressed as all hell to be leaving my little social bubble I had been entrenched in for the past four years, unable to even come close to holding a conversation with anyone outside of my immediate group of friends, the future outside of school seemed bleak to me. Until one night totally changed the trajectory my life was on at the time. I can't say I wouldn't have gotten to that place naturally, but I can say that if so, then this experience definitely streamlined the process.

    I don't remember exactly how it happened, all I know is that I was supposed to be going to Las Vegas with a couple friends and trip on psilocybin mushrooms for the first time, having never tried a psychedelic previously. That weekend me and another friend procured some shrooms. This other friend didn't purchase any, so I gifted him some of what I bought in exchange for his company. After this I headed home, and being apprehensive of the experience only ingested half of the shrooms. What followed was an interesting but underwhelming experience, in which I experienced only minor visuals and a bit of euphoria. However I still had half of the mushrooms left.

    Fast forward three days, and I lacked the self control to wait until my tolerance diminished completely. I took the rest of them, hoping for the mild euphoric experience I had experienced a few days prior, boy was I in for a surprise. My parents weren't home and I had the house to myself, and as I felt them coming on I walked around looking at the mild visuals I was again experiencing. For this to make sense to anyone who's not me I need to get into a bit of context. I was raised in a catholic household, and was taught that I would one day go to heaven. Even as a child this never particularly resonated with me, as the concept didn't make much sense, however being a young impressionable kid I went along with it.

    In this moment however, all of those memories of being a scared child came rushing back. I finally thought about what exactly it meant that I would die one day, and holding the beliefs I did, that meant the end. Empty. Eternal. Nothingness. I mourned the fact that I'd never experienced extended physical contact with another human being since I was young, and at that point in time saw no future in which I could ever land myself a girlfriend/spouse. Before this point, I was for lack of a better word "comfortable" with myself. I had accepted that I would never see even the tiniest bit of relief from the case of social anxiety which was ruining my life. In that moment however, that all changed. From that point onward, I had a new goal in life. To get whatever the fuck I want, because I'm going to die one day so none of it will have mattered anyway right? At the top of that then list, beat that social anxiety. Now, things were not all fun and games. For 6-7 months after that I dealt with a crippling fear of dying, which invaded every corner of my life. There were times where I'd be having the time of my life, then suddenly remember that said life would one day end, completely taking me out of the moment into the cold embrace of fear and depression. But that same fear drove me—anytime I felt anxious in a social setting I would just think that simple thought, and it made things easier.

    This is somewhat difficult to properly convey to people, as everyone knows they're going to die. Yet this experience changed the way I viewed that concept, with it still affecting the way I think, although now I no longer fear the inevitable. The drive to improve myself against all odds and by any means remained. If this night had never happened I truly believe that I would be a different person today, still hiding in my comfort zone. Never taking any chances in life. It is important to note that Shrooms absolutely did NOT cure my social anxiety, they simply motivated me to get up off my ass and do something about it in a way which nothing beforehand ever did. I still have a relatively minor case of social anxiety (especially compared to how severe it was before) and I think to some extent I always will, however I know I can still improve. Thanks in part to my old friend Psilocybin.

    Now I don't have as much to say about LSD, however I've used it in the past at times where I've been slipping up in some of the habits I've set up for myself to further my personal growth, and it's thrown me back on track each time.

    Don't fall for the hype about psychedelics, they aren't some magical solution to all of your problems. They have, however, been beneficial to me in more subtle ways, such as a psilocybin experience giving me the motivation to improve myself. LSD is perhaps a bit more "recreational," though it too can be a powerful tool. TEST YOUR ACID, BE SAFE.

    https://steemit.com/socialanxiety/@s...ybin-mushrooms
    Last edited by mr peabody; 13-10-2018 at 01:22.
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    #27
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    Ketamine effective as maintenance treatment for anxiety


    In patients with treatment-refractory anxiety who responded to ketamine, weekly maintenance doses over 3 months were well tolerated and significantly improved social and work functioning, according to a small study published online in the Journal of Psychopharmacology.

    The findings suggest maintenance ketamine may be a therapeutic alternative for that patient population, researchers concluded.

    “Their experience of ketamine treatment enabled them to make substantial changes to their lives (employment, study, making friends, engaging socially, and traveling),” a Psychiatric News Alert article quoted from the study. “Reduced anxiety meant that everyday tasks were less onerous. Most patients reported an increase in their ability to concentrate, leading to improvement in their functionality.”

    Ketamine quickly eases depression, but questions remain

    The anesthetic agent ketamine and other glutamatergic drugs produce rapid antidepressant effects in humans, reports a new evidence review published online in the Harvard Review of Psychiatry. However, questions about the agents and their ramifications persist.

    “This paradigm shift lends additional urgency to the development of novel treatments for major depressive disorder and bipolar depression, particularly for patient subgroups that do not respond to currently available therapies,” wrote Carlos A. Zarate Jr., MD, and colleagues at the National Institute of Mental Health.

    In their review, Dr. Zarate and colleagues reported that ketamine has demonstrated antidepressant response in patients with treatment-resistant major depressive disorder within 2 hours of intravenous injection. Peak effects in the population occurred at 24 hours.

    Why not make ketamine a first-line treatment?

    Evidence suggests ketamine may also ease suicidal thoughts, according to the review. In people with treatment-resistant bipolar depression, ketamine combined with other medications has demonstrated quick antidepressant effect.

    "Consequently, some providers are already using ketamine for severe or treatment-resistant depression," the authors point out. "However, such use is off-label, unstandardized, and unregulated, and questions about the drug’s side effects and abuse potential remain."

    “Efforts are underway,” they added “to bring ketamine to market, standardize its use, and determine its real-world effectiveness.”

    Psychiatrists issue 'much-needed' consensus on ketamine for mood disorders

    Esketamine, another glutamatergic medication, has received breakthrough status from the US Food and Drug Administration for patients at imminent risk of suicide, they noted.

    In another review, also published online in the Harvard Review of Psychiatry, a study team evaluated neuroimaging research on ketamine’s effects on brain areas involved in depression.

    "Ketamine may acutely disable the emotional resources required to perpetuate the symptoms of depression,” reported Cristina Cusin, MD, of Massachusetts General Hospital in Boston, and colleagues. "The drug may also increase emotional blunting as well as boost activity in reward processing," they wrote.

    The open-label study involved 20 patients with generalized anxiety disorder and/or social anxiety disorder who responded to ketamine in a previous ascending-dose study. Patients in the maintenance treatment study had 1-2 weekly doses of 1 mg/kg of ketamine injected subcutaneously for 3 months.

    Just 1 hour after injection, ratings on both the Fear Questionnaire and the Hamilton Anxiety Rating Scale dropped 50%, researchers reported. Over the course of the study, mean scores on the Clinician Administered Dissociative States Scale decreased, from 20 points at week 1 to 8.8 points at week 14.

    Adjunctive intranasal esketamine eases Treatment-Resistant Depression

    In patients with treatment-resistant depression (TRD), twice-weekly intranasal esketamine added to oral antidepressant therapy produced rapid and meaningful improvement in depressive symptoms in a phase 2 double-blind, randomized, placebo-controlled trial.

    Dr. Ella Daly, of the Department of Neuroscience, Janssen Research & Development in Titusville, New Jersey, and colleagues reported the findings online December 27 in JAMA Psychiatry.

    “The results of the study by Daly and colleagues demonstrate the considerable promise of combining a compound with rapid antidepressant effects with intranasal delivery,” write Dr. Daniel Quintana and colleagues from University of Oslo, Norway, in a linked editorial.

    Dr. Daly and colleagues tested 28-mg, 56-mg, and 84-mg doses of esketamine nasal spray given twice weekly as an adjunct to existing oral antidepressant therapy in 67 patients with TRD.

    All three doses of esketamine produced a rapid antidepressant effect superior to placebo, as evidenced by significant changes in the Montgomery-Asberg Depression Rating Scale (MADRS) total score. The score declines were -4.2, -6.3 and -9.0 for the 28-mg, 56-mg and 84-mg doses, respectively.

    “Improvement in depressive symptoms persisted over the open-label phase, despite reduced dosing frequency, and for up to 2 months after cessation of esketamine dosing,” the investigators note.

    The three esketamine doses appeared to be safe, with no new or unexpected safety concerns

    Dr. Quintana said it is “reassuring to learn that no psychotic symptoms were observed in the trial; however, patients with psychotic disorders or major depressive disorder with psychosis were excluded from the study. The most common adverse effect, dissociative symptoms, fits with the known effects of ketamine, and should be further clarified before starting routine use in clinical practice,” they write. "In addition, several issues related to long-term use, including the potential for addiction and adverse effects, need to be carefully assessed in future studies," they say.

    “Given the early stages of research in esketamine treatment of depression, it is important to be cautious. We look forward to further research developments of intranasal esketamine as a novel treatment for depression given the crucial need for better antidepressants,” write Dr. Quintana and colleagues.

    "About 1/3 of patients with major depressive disorder do not respond to current treatment options," Dr. Husseini Manji, Janssen's Global Head of Neuroscience Therapeutic Area, said in a news release. "The results of this study reinforce the potential of esketamine as a treatment for patients with treatment-resistant depression, and support further clinical research, providing hope for people in need. If approved by the FDA, esketamine would be one of the first new approaches to treat refractory major depressive disorder available to patients in the last 50 years."

    “Phase 3 studies in treatment-resistant depression are ongoing and we are working on finalizing those studies now,” Dr. Daly told Reuters Heath by email.

    Of the 20 patients enrolled in the study, 18 completed all 3 months of maintenance treatment—and all reported improvements in social and work functioning, Psychiatric News Alert reported. Two weeks after their last ketamine injection, 8 patients experienced some return of anxiety (5 experienced full re-emergence). Three months after maintenance treatment ended, 5 patients remained well.

    Nausea, dizziness, and blurred vision were the most common adverse events during the study.

    https://www.psychcongress.com/articl...atment-anxiety
    Last edited by mr peabody; 28-09-2018 at 11:22.
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    Iboga found to cure depression, anxiety and PTSD

    Ibogaine is a powerful psychedelic from West Africa that has been in use for centuries in traditional healing ceremonies. It can be used in its traditional form from the root bark of the plant (known as iboga), or in the laboratory-isolated form of ibogaine which only contains the central psychoactive substance (known as ibogaine). Today iboga is best known for its miraculous ability to cure or drastically reduce addiction to substances like alcohol, crack cocaine, and heroin in a single treatment. It can also help people overcome addiction to prescription opiates such as morphine, methadone, Vicodin, Percocet, and OxyContin.

    While this may sound too good to be true, scores of personal testimonies and clinical research is backing up this claim, and iboga treatment centers are popping up all over the world specializing in treating addiction, post traumatic stress, and mood disorders. Iboga is renowned for its ability to cure addiction by revealing the fragmented pieces of a person’s past and personality over the course of a long, intense, and ultimately cathartic psychedelic experience. After finishing iboga treatment, patients report a feeling of rebirth that allows them to see the world in a totally new light and leave behind their old destructive patterns of behavior for good.

    One fascinating common experience that many people report in iboga treatment is the ability to see your life played out in front of you on a series of 3-dimensional screens that you can zoom into and out of. The “spirit” of the iboga plant is often present during this process, lovingly but authoritatively guiding the person to see the lessons that are in front of them- how they have been out of balance, how their behavior has hurt others, and where they can improve their capacity for joy, wholeness, and health.

    With so many reported cases of incredible success with iboga treatment, western doctors and scientists are taking note and performing clinical studies to better understand how iboga works. According to doctor C.M. Anderson of Harvard Medical school, iboga has “unique neuropharmacological and psychobiological properties” that make it particularly conducive to treating chemical dependency. Iboga has a profound ability to guide people through a journey of self-reconciliation that is often at the heart of addictive behaviors and other disorders. With proper integration of this experience and supervised aftercare such as with a recovery coach, these transformative experiences can have a permanent positive effect on a person’s life.

    While many undergo ibogaine therapy for serious drug addiction, this treatment can also trigger recoveries from many other psychological issues including depression, anxiety, and trauma. The drug’s deeply personal and illuminating nature also allows patients to let go of different types of patterns not related to drug use that may be equally difficult for them to break. This is especially life changing for victims of chronic depression, anxiety disorders, and post-traumatic stress disorder (PTSD), which often cause such intense emotional stress that recovery seems impossible. For people who suffer from these terrible chronic afflictions, iboga offers a bright ray of hope backed by hundreds of years of traditional use, many thousands of successful anecdotal cases, and more and more scientific validation.

    https://psychedelictimes.com/learn-more-iboga/
    Last edited by mr peabody; 28-09-2018 at 11:23.
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    Therapy didn't help my anxiety, so I turned to psychedelics

    I am in some kind of hole, I told my therapist. I was trying to work out what was happening to my mind. Months of traumas - family issues, the violent death of a friend, the implosion of my relationship, had, like a slow poison, seeped into my life until I felt paralyzed. I was trapped in a loop of discursive, self-critical thought. I am a freelance journalist, but I found myself unable to take on new assignments and, inexplicably, unwilling to invoice for finished work. After our session, my therapist eyed me with indifference and handed me forty photocopied pages on cognitive behavioral therapy as he shuffled me out the door. I got the sense that approach was going nowhere.

    I had researched meditation, exercise, dietary changes and other ways to prevent myself from slipping further down the hole. But the most intriguing method I came across was psychedelic drugs, which had, in recent studies, shown great efficacy in treating depression, anxiety and PTSD. My underwhelming experience with therapy had left me with the kind of hopelessness that breeds desire for radical solutions. I opened my laptop and googled Toronto psychedelic drugs.

    6 weeks later, on a Sunday in February, I was lying on the floor of a woman's apartment in the east end, wrapped in a Mexican blanket and weeping uncontrollably. I'd met the woman a few hours earlier. She was a shaman, a spiritual healer who practices South American plant medicine. In her pre-shamanic life, she suffered from a severe drug addiction, was homeless and hadn't spoken with her family for a decade. Eventually, she made her way to South America, where she trained in the shamanic arts, conducting ceremonies using a psychedelic tea called ayahuasca.

    The author Michael Pollan, in his recent book on psychedelics, describes the concept of ego dissolution, which is an often-reported and now scientifically supported effect of potent psychedelics. Scientists at Imperial College London have observed that activity in the brains Default Mode Network, the system responsible for building a sense of self and reflecting on the self's nature, can drop dramatically during a psychedelic trip. The default mode network is vital to healthy neural function, acting as the brains central coordinator. But its also a real son of a bitch, the devil on your shoulder, the author of hopelessness and self-blame. Conditions like anxiety and depression can be associated with a default mode network run amok and, according to proponents of psychedelic treatments, a little dissolution of the ego can be a good thing.

    The shaman said she had personally synthesized the medicine I was about to take, DMT. She produced a glass pipe and explained that I was to take five hits. "On number three, you'll tell me you've had enough, and I'll tell you to keep going," she said. If you have ever been close to blackout drunk and seen the world spin uncontrollably around you, then you know what the third hit of DMT is like. The shaman guided the pipe to my mouth for the fourth and then fifth hits, and suddenly I was laid out on my back.

    Everything turned black, as though I was watching a blank screen, except that there was no me watching. The blackness was just there, happening. I was vaguely aware of the self, but only insofar as I knew that I was aware at all. Then a pool of green, red and yellow fire appeared, swirling around what looked to be a medieval helmet.

    This was taking place within the confines of my brain, yet it was completely involuntary - decisive, overwhelming subjugation of the ego. I started to feel some sense of self again, in the form of two distinct emotions: I was in awe of the fire and terrified of the helmet. I felt I would fall into it and that I was going to die. The image shattered. The pieces re-emerged as a pattern of purple and black shields, then disappeared. Soon, I was aware of the shamans hand on my arm, and I realized that I had been weeping. Respira, she whispered. Breathe.

    She was fascinated by what I told her about the helmet and shields. Like all of our emotions, anxiety is a chemical effect in the brain, one that likely evolved over millennia because it served a purpose in our survival. It was a kind of armor, meant to protect us. But when the mind surrenders control, anxiety can become a cage. The helmet made some sense.

    Sitting under the fluorescence of the 501 streetcar on my way back home, I thought more about the helmet and how it had shattered before it could take me. Perhaps my anxieties could shatter, too, if I could manage to observe them from the outside. These are realizations that don't require DMT or shamans, of course. But the trip brought shape and clarity to what I had been feeling. I cant say that the fear and the panic have vanished. Sometimes they wake me up early in the morning, or accompany unexpected moments of disappointment or failure. But they seem more brittle now, with obvious cracks through which I can see a world that is a little lighter.

    https://torontolife.com/city/life/th...wers-expected/
    Last edited by mr peabody; 02-10-2018 at 22:07.
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    Ann and Sasha Shulgin


    Psilocybin investigated for its anxiolytic (anti-anxiety) properties

    Recently, psilocybin received recognition as a potential treatment for anxiety. A pilot study conducted explored the ability of psilocybin to reduce anxiety in individuals with advanced stage cancer. Although a small study and exploratory in nature, it suggested that psilocybin could have some benefit in reducing anxiety and improving mood in patients with a terminal illness.

    In a study due to be published soon in Biological Psychiatry, a research group in Switzerland explored a potential mechanism for reduced anxiety after psilocybin administration. The authors, Kraehenmann et al., administered psilocybin or placebo to a group of participants. Then, they monitored the participants' brain activity using functional magnetic resonance imaging (fMRI) while the subjects completed a task that generally increases activation in an area of the brain called the amygdala. The task involved viewing a series of pictures; half of the pictures presented negative stimuli like a car accident, and the other half presented neutral pictures like everyday objects or scenes from daily life.

    The amygdala is an almond-shaped collection of nuclei in the temporal lobe (there are actually two amygdalae--one in each hemisphere). Increased activity in the amygdala has been associated with emotional reactions, and especially with fear and anxiety. Hyperactivity in the amygdala has also been observed in depressed patients, and treatment with selective serotonin reuptake inhibitors (SSRIs) has been found to reduce that hyperactivity. This suggests that increased activity in the amygdala may also play a role in symptoms of depression.

    Kraehenmann et al. found that psilocybin administration improved mood and decreased anxiety. But the study also offered some insight into what might be causing that reduction in anxiety. After taking psilocybin (as compared to placebo), activity in the right amygdala was reduced while viewing negative images, and activity in the left amygdala was decreased in response to both negative and neutral images.

    Psilocybin is thought to act as an agonist at serotonin receptors, meaning it increases serotonin transmission. Thus, it may be that antidepressants like SSRIs that act on serotonin--at least as part of their mechanism--have something in common with psilocybin. And, it suggests that perhaps psilocybin should continue to be investigated for its antidepressant and anxiolytic (anti-anxiety) properties.

    https://www.neuroscientificallychall...d-the-amygdala
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    Psychedelic medicine for anxiety

    After the DEA’s Controlled Substances Act of 1970 put hallucinogens and cannabis in Schedule 1, research on both essentially ended.

    But now the authors describe two recent clinical studies that used psilocybin along with psychotherapy and produced positive results in treating anxiety and depression.

    Both are randomized placebo-controlled studies recently completed by groups at Johns Hopkins University (JHU) and at New York University (NYU). Study results are in press. Both are reasonably large phase II trials of psilocybin-assisted psychotherapy in patients suffering from cancer-related psychosocial distress.

    “These two studies,” the authors wrote, “represent the first sufficiently powered, formal double-blind, placebo-controlled assessment of a psychedelic agent for therapeutic effect using modern clinical approaches and assessment instruments.”

    "Both studies found remarkable efficacy. That is unprecedented for cancer-related psychosocial distress with any currently available conventional therapies,” they added.

    The JHU study investigated the effects of a high oral psilocybin dose with a low dose as a placebo on anxiety or depressive disorders caused or worsened by the cancer diagnosis.

    Rating scales showed sustained positive effects on anxiety and depression at six months, and an immediate post-session mystical experience (a subjective experience involving feelings of internal and external unity, sacredness, positive mood, transcendence of time and space, among others) score correlated strongly with positive therapeutic results.

    The study showed that a single psilocybin dose, given under supportive conditions to screened and prepared participants, produced substantial and enduring decreases in anxiety and depression in patients with a life-threatening cancer diagnosis.

    http://cherylpellerinscience.com/pro...ty-depression/

    -----

    MDMA and PTSD
    *

    MDMA interacts with a transporter in the brain that causes the release of serotonin, which in turn causes the release of other neurotransmitters and hormones. For people who might otherwise flee psychotherapy, MDMA reduces fear and increases trust and empathy. MDMA is also mildly stimulating rather than sedating. The overall effect is to calm patients and help them engage with a therapist about difficult experiences. Sessa likens MDMA to a life jacket.

    U.S. psychiatrist Michael Mithoefer leads clinical trials studying MDMA for PTSD. In an initial trial, Mithoefer and colleagues worked with patients who had PTSD for an average of 20 years, mostly from sexual trauma. The patients had undergone previous psychotherapy for an average of almost five years and were not helped by conventional antidepressants. They received MDMA or a placebo two to three times, with doses one month apart, as part of eight-hour sessions with two therapists followed by an overnight stay at the clinic for continued monitoring.

    Going through the psychedelic experience, patients could focus inward and stay quiet as they wished or talk with the therapists. They also had extensive preparatory and follow-up psychotherapy sessions. Of 12 patients who received MDMA, 10 of them (83 percent) showed significant relief of their PTSD symptoms. In the placebo group, only two out of eight patients (25 percent) showed improvement with the same psychotherapy support.

    Other studies show similar positive results, although “it is hard to have an effective ‘blind’ with this type of substance,” Mithoefer concedes, because patients can usually tell whether they’ve been given a placebo or the real thing.

    *From the article here: https://inchemistry.acs.org/content/...nic-drugs.html

    Last edited by mr peabody; 21-10-2018 at 07:49.
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    Least anxiogenic psychedelics


    -2C-I and 4-HO-MET are both pretty good that way, IME.

    TheAzo

    2C-C is by far the least anxiety provoking psychedelic IMO, 2C-B coming in close second. I also think Mescaline can be very friendly.

    -<SpaceHead>

    2C-C is magical in this respect. 4-HO-MET, 4-HO-MiPT or 4-HO-MPT are all wonderfully colorful without being too anxiety inducing.

    -reformer

    5-MeO-DMT. I love it, it is almost like benzo and it gives me state of extreme peacefulness. 2C-I is nice and enjoyable!

    -allium

    My girlfriend suffers from anxiety and is taking citalopram for it, and she says 4-AcO-DiPT produces no anxiety for her.

    -MachoSavage

    2c-c by a wide margin. Its hard to even imagine anxiety on 2c-c at less than about 60mg.

    -egor

    2C-B and 4-AcO-DMT (very very similar drugs) are very easy to handle mentally, 2C-B makes me euphoric and takes me "along for the ride" without any emotional effort.

    -danceofdays

    5-Me0-DALT is a great psych for a new tripper. It's not heavy mentally or visually. But the bodily euphoria is something else, and it's a great introduction to the profoundness.

    -Carver Slice

    Well, I tried the 4-AcO-DMT tonight at 10mg. No anxiety or negative sides at all!

    -Reefers

    Mescaline. Extremely clear headspace, warm visuals that aren't overwhelming. Very much like a warm blanket over a psychedelic.

    -SpecialK_

    I would have said 2C-C earlier but after trying a few tryptamines I would say 4-HO-DiPT.

    -Solipsis


    http://www.bluelight.org/vb/threads/...ic-Psychedelic
    Last edited by mr peabody; 01-10-2018 at 07:52.
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    Could psychedelic drugs treat depression and anxiety?


    Psychedelic such as LSD and ayahuasca change the structure of nerve cells, causing them to sprout more branches and spines, UC Davis researchers have found. This could help in "rewiring" the brain to treat depression and other disorders.

    Scientists have demonstrated how psychedelic drugs such as DOI, DMT, and LSD, cause structural and functional changes in brain cells that could feasibly be harnessed to help treat depression and related disorders. Depression is known to cause the atrophy of neurons in the prefrontal cortex (PFC) in the brain, and in vitro and in vivo studies by researchers at the University of California, Davis, have found that different classes of psychedelic drugs increase the numbers of neuronal branches, or dendrites, as well as the density of dendritic spines and synapses in cortical neurons. Some psychedelics tested, including LSD, demonstrated structural effects that were even more potent than those of the anesthetic ketamine, which over the last two decades has been the subject of intense research as a potentially fast-acting antidepressant for people who don’t respond to existing therapies.

    “People have long assumed that psychedelics are capable of altering neuronal structure, but this is the first study that clearly and unambiguously supports that hypothesis,” comments research head David Olsen, Ph.D., assistant professor of chemistry, biochemistry and molecular medicine at UC Davis. “What is really exciting is that psychedelics seem to mirror the effects produced by ketamine.”

    The UC Davis team has coined the term "psychoplastogen" to describe neuronal plasticity-promoting compounds, and reports on its work in a paper, entitled “Psychedelics Promote Structural and Functional Plasticity,” which is published today in Cell Reports.

    Multiple studies have demonstrated that the pathophysiology of depression and related disorders is associated with atrophy in PFC neurons and with “structural changes, such as the retraction of neurites, loss of dendritic spines, and elimination of synapses,” the researchers write. "One of the hallmarks of depression is that the neurites in the prefrontal cortex—a key brain region that regulates emotion, mood, and anxiety—those neurites tend to shrivel up," Dr. Olson explains.

    Finding compounds that can promote structural and functional plasticity of neurons in the PFC could feasibly offer a general solution to treating such disorders, but the few compounds identified so far have “significant drawbacks,” the team continues. Of these, the most promising, ketamine, has shown “remarkable clinical potential as a fast-acting antidepressant,” even for treatment-resistant populations. Studies in animals have shown that the compound can promote the growth of dendritic spines, boost production of synaptic proteins, and bolster synaptic signaling.

    Some clinical studies have shown that, like ketamine, serotonergic psychedelic drugs can also have long-lasting antidepressant and anxiolytic (anti-anxiety) effects, including in treatment-resistant patients, and one, MDMA recently received FDA breakthrough therapy designation for treating post-traumatic stress disorder (PTSD). However, while such serotonergic psychedelics have demonstrated promising anxiolytic and antidepressant properties, how they work isn’t yet understood, and questions about their potential safety has held back clinical use. "These are some of the most powerful compounds known to affect brain function, it's very obvious to me that we should understand how they work," Dr. Olson states.

    This similarity between the effects of serotonergic psychedelic drugs and ketamine, both in clinical studies and in animal models, led the UC Davis team to reason and test whether the therapeutic effects of these different drugs might stem from similar mechanisms of action, which promote structural and functional plasticity in cortical neurons.

    Initial in vitro studies using rodent cortical cultures showed that just about all of the tryptamine, amphetamine, and ergoline-type psychedelic compounds tested promoted neuritogenesis, with many demonstrating more potent effects than ketamine. In vivo evaluation in Drosophila larvae then confirmed that the drugs significantly increased dendritic branching of sensory neurons.

    “…our results demonstrate that psychedelics can promote changes in neuronal structure across vertebrate (rats) and invertebrate (Drosophila) species, suggesting that they act through an evolutionarily conserved mechanism.”


    Loss of dendritic spines is another hallmark of neuropsychiatric disorders such as depression, and in a separate set of microscopy studies the UC Davis team showed that treatment of mature rat cortical cultures with DOI (amphetamine), DMT (tryptamine), and LSD (ergoline) increased the numbers of dendritic spines, and also promoted the formation of synapses, resulting in increased synaptic density. Follow-on in vivo studies in adult rats also showed that treatment with DMT led to increases in dendritic spine density in prefrontal cortical neurons 24 hours after dosing. These results were comparable to those resulting from a similar dose of ketamine. DMT-induced increases in dendritic spine density were also linked with increased postsynaptic electrical activity. “Because the half-life of DMT is exceedingly short (~15 min), these results confirm that structural and functional changes induced by DMT persist for hours after the compound has been cleared by the body,” the team said.

    Prior studies have demonstrated that the behavioral effects of ketamine are dependent on brain-derived neurotrophic factor (BDNF), which is also known to play a role in neuritogenesis and spinogenesis. The team’s studies also demonstrated that inhibiting BDNF’s high-affinity receptor TrkB (or tropomyosin receptor kinase B) blocked the ability of either the psychedelic drugs or BDNF itself to stimulate neuritogenesis and spinogenesis.

    Activation of TrkB promotes mechanistic target of rapamycin (mTOR) signaling, “which plays a key role in structural plasticity, the production of proteins necessary for synaptogenesis, and the effects of ketamine,” the authors comment. Then they found that treatment with the mTOR inhibitor rapamycin also blocked the ability of psychedelic drugs to promote neuritogenesis, “thus confirming that mTOR activation plays a role in the plasticity-promoting effects of classical serotonergic psychedelics."

    In a final set of studies the researchers investigated whether the serotonin 2A (5-HT2A) receptor, which is primarily responsible for the hallucinogenic effects of classical psychedelics, played any role in the plasticity promoting effects of DOI, DMT, and LSD. They found that chemically inhibiting 5-HT2A completely blocked psychedelic drug-related neuritogenesis and spinogenesis.

    “Our work strengthens the growing body of literature indicating that psychoplastogens capable of promoting plasticity in the PFC might have value as fast-acting antidepressants and anxiolytics with efficacy in treatment-resistant populations and suggests that it may be possible to use classical psychedelics as lead structures for identifying safer alternatives."

    "Ketamine is no longer our only option,” Dr. Olson notes. “Our work demonstrates that there are a number of distinct chemical scaffolds capable of promoting plasticity, like ketamine, providing additional opportunities for medicinal chemists to develop safer and more effective alternatives.”

    “We have demonstrated that the plasticity-promoting properties of psychedelics require TrkB, mTOR, and 5-HT2A signalling, suggesting that these key signalling hubs may serve as potential targets for the development of psychoplastogens, fast-acting antidepressants, and anxiolytics,” the authors conclude. “Taken together, our results suggest that psychedelics may be used as lead structures to identify next-generation neurotherapeutics with improved efficacy and safety profiles.”

    https://www.genengnews.com/gen-news-...xiety/81255910
    Last edited by mr peabody; 06-10-2018 at 07:02.
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    #34
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    LSD liberated me from the prison I had built for myself


    I was 20 years old, freshly dropped out of college, and a couple months removed from my first drink. I bloomed into rebellion later than most, because I grew up in the shadow of my sister’s addictions, multiplicitous, but primarily oriented towards methamphetamine. I’d always seen all drugs as shades of the same.

    My panic attacks began on my first day of kindergarten. By 2nd grade, I’d taught myself how to fake sick well enough that I missed half a semester with “allergies.” When middle school rolled around, my anxieties manifested in a physical way. My blood cell counts plummeted. The doctors ran every test imaginable. I laid in bed all day. I wore a surgical mask when I left the house. A cold would kill him, the doctor whispered.

    Suicidal thoughts started when I was 16. I had scarcely made it through my freshman orientation when I swallowed a bottle of pills and awoke in a hospital. My scholarship was revoked, my invitation to an education was rescinded, and my family was scared to look me in the eye.

    So now here I was, a year later, as anxious and depressed as ever. I’d tried a dozen different SSRIs and mood stabilizers. Nothing worked.

    I was working at a coffee shop, and I’d started hanging out with a hippie coworker named A. I’d text him late at night when I found myself spiraling and he’d bring me a gram of pot and we’d smoke on my porch until my eyes grew heavy and I could sleep.

    When he mentioned LSD to me for the first time, I scoffed. I’d seen the cartoonish depictions of acid trips in movies, and I’d heard all the scare-lines: it stays in your system forever, it drives you mad etc. But of course, desperation can awaken in a man any number of possibilities of which he never thought himself capable. A called it spiritual. I was so tired of hurting.

    2 weeks later, he showed up at my apartment with tin foil and a book called Be Here Now. I placed the stamps on my tongue and thumbed through the book. I couldn’t make head or tail of it. All the hippie jargon and imprecise language. Why had he given this to me? What was I hoping to find?

    I laid in my bed and turned out the lights. I began to see trails of light across the dark corners of my bedroom. I felt stirred to stand. I drifted towards the window, but instead of urban blight, it was pure light, living water. I floated atop the water of the endless ocean. Not a wave or ripple as far as the horizon. A place of strange and perfect calm.

    My busy head was quieted. I had no fear of the future, or regret of the past. I lived in the timeless present. My anxieties of inadequacy disappeared. My ego stretched and snapped, my costume flew off, and all that was left was pure awareness. I sat in boundless beauty. It was a miracle, and it was totally ordinary. When I opened my eyes, I was back in my room. The song played itself out. I had slipped out of my pain for a lifetime and fallen back into my body here, three minutes later.

    I rushed to the mirror, surveyed the vehicle that carried my pure consciousness across time and space, and for the first time in my life, I felt total compassion for him. I forgave my body for its asymmetry; I forgave my brain for its limitations; I gave up the narratives I’d created. And it liberated me from the prison I’d built for myself.

    4 years since that trip, I’ve had no major depressive or manic episodes. I haven’t taken a psychedelic in two years, and I’m no longer prescribed antidepressants. I’m working to cultivate a daily meditation practice, and I’m lighter, happier, and more stable than I ever thought possible.

    Like a fish can’t see water, I couldn’t see that the point was right in front of me. Everything is everything, and I am part of the unfolding. Call it God, the simulation code or the quantum fabric of our physical world. Whatever the name, the good, the bad, the pain, the ecstasy, it’s all divine.

    I can’t go back and teach my younger self that lesson, so I’m writing it down. I hope this finds someone at just the right time and place to receive it.

    https://www.psymposia.com/magazine/l...lt-for-myself/
    Last edited by mr peabody; 01-10-2018 at 09:28.
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    #35
    Bluelighter mr peabody's Avatar
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    Treating anxiety with psychedelics

    Many people find their day-to-day experience of life is filled with anxiety, limiting the activities they do and the enjoyment they have in life. Psychedelics like mushrooms and LSD have been used for decades to treat anxiety disorders and to reduce anxiety levels.

    For some, these substances seem to directly alleviate feelings of anxiety, even at very low doses. For others, psychedelics help them explore the root causes of their anxieties and find peace with them, a new touchstone for letting go of anxiety.

    This description may sound abstract to someone suffering from anxiety. The healing process can be a little difficult to convey. Recent clinical research has shown dramatic reductions in anxiety even after a single psychedelic experience. Psilocybin enables patients facing the anxiety of terminal illness to embrace their fate and find peace with their loved ones.

    Here is one woman's story of being treated with mushrooms as she was facing death, described in a New York Times article:

    Norbert Litzinger remembers picking up his wife from the medical center after her first session and seeing that this deeply distressed woman was now "glowing from the inside out." Before she died, she described her psilocybin experience on video:

    "I felt this lump of emotions welling up . . almost like an entity," Sakuda said, as she spoke straight into the camera. "I started to cry . . Everything was concentrated and came welling up and then . . it started to dissipate, and I started to look at it differently . . I began to realize that all of this negative fear and guilt was such a hindrance . . to making the most of and enjoying the healthy time that I'm having." Sakuda went on to explain that, under the influence of the psilocybin, she "came to a very visceral understanding that there was a present, a now," and that it was hers to have.

    What is so remarkable is that even a single dose of a psychedelic substance can create long lasting changes, reducing anxiety, depression, and creating more emotional openness. LSD, MDMA, and psilocybin have all been studied for anxiety reduction. Remember that a psychedelic experience can sometimes produce anxiety or can focus the mind on sources of anxiety, as part of the process of addressing the root causes. Starting with small doses and following all the safety guidelines can help reduce anxiety.

    http://howtousepsychedelics.org/anxiety/


    Last edited by mr peabody; 09-10-2018 at 07:29.
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    Psilocybin healed me from crippling anxiety

    When I was in my late teens I first experienced my first real bout of depression, precipitated by the social isolation that came from acute social anxiety. I felt insecure and inadequate amongst my peers, so avoided socializing completely unless alcohol was involved.

    Fast forward through my 20’s and early 30’s and the rut I developed as an adolescent had stayed with me. The pattern was work, where I felt safe and in control, and then evening drinking in the bars and clubs as a social outlet. I avoided anything social where drinking would be unacceptable, I felt as though I needed it to mask my anxiety.

    Throughout those years of many extremely drunken nights, I accumulated what I can only describe as a ball and chain of shame. From the many forgotten nights, fights, arrests and broken bones I increasingly looked back at my past and only saw failure. Bouts of depression were a recurring feature, broken up by periods of welcome but fragile relief when the latest SSRI prescription temporarily lifted my mood.

    At 33 I left my fairly respectable 4-year position as Head of Technical at a media company, due to stress and the desire to take time out to try and ‘fix’ my issues, I left with no plans other than to ‘work on myself.’ I ended up moving back to my mum’s house where the following events took place.

    I had been out of work for a couple of months and Instead of a life of self-development and exploration, stagnation and rumination had firmly set in. Christmas came, and went, and as the days passed I feel ever deeper in to a dark and lonely place…

    I became extremely socially anxious, terrified of the future and resentful of the past. I was rendered house bound or even bed bound for much of the time. The anxiety was so crushing that had to force myself just to eat a bowl of cereal each day, and when I was out of bed I paced around like a caged animal, the suffering and fear were intense.

    As the days, weeks and months fell through my fingers and I had failed to pull myself out of the hole, the feelings of hopelessness grew. The thought of suicide advanced from a fantasy to a considered reality. Over my life I had tried SSRI’s, MAOI’s, CBT, counseling, drama therapy, high does fish oil, transcranial direct current stimulation, running and more and now I had got to the point where I thought I had run out of options and hope. And then, after more than six months of blackness, I had an incredible experience.

    It was the darkest night of my life. Followed by a kind of awakening. Early on in the day, I was running through the park feeling full of pain, fear and shame, desperate to escape the never-ending crippling anxiety and depression. I clasped my hands together and asked God/the universe (even though I consider myself an atheist) for help and guidance to see me through and to help me learn to accept myself…

    That night I decided to take some magic mushrooms. I had read about their healing potential with depression and PTSD so with little else to try I swallowed 2 grams of ‘Golden Teacher’ mushrooms and retired for the evening to bed.

    An hour later I was lying in bed with a deep sense of dread, my mind racing over the past. All my foolish mistakes and drunken incidents, all the bitterness and fear I had felt. All the resentment towards my family for the pain of the past. All my social anxiety and fear of judgment, embarrassment or rejection, and all my foolish and selfish behavior.

    At that moment I felt my heart break and my soul die. In that moment I felt sure I was doomed, that it was too late to live the life I had once imagined or be the person I would have liked to be. All hope was lost…

    As I lay in bed in the near dark, puffing on my vape pen, the layers of water vapor stratified and descended over the room like an eerie mist. In the dull light, my bed sheets appeared like a death shroud, draped over my torso and knees, ossified and covered in cobwebs. On the back of the door hung a long black jumper and I suddenly felt as though an angel of death was standing there watching over my corpse, signaling the end for me.

    I gasped in a panic, shocked at the feeling of annihilation. In the midst and terror off feeling my whole being and identity crumble, I sat up and focused my mind intensely. Then came a voice, from what seemed outside of me, a voice of strength and wisdom. It said ‘no more blame.’ All of a sudden, what felt like a light and energy from the universe, lit up my body and filled my empty corpse with life. My heart burst open, with an incredible fire, and for the first time, I understood.

    I started sobbing and cried ‘thank you’, ‘thank you’ with a feeling of gratitude so powerful I had never felt before. I was overjoyed to be alive, filled with feelings of love; for my family and friends, and all other beings finding their way through their short time on this earth.

    I bowed down across my bed, hands clasped, in astonishment, bursting with gratitude, humility and love. My deep feelings of shame dissolved as I caressed the my face softly. With tears of joy I declared ‘I am human, I am flesh and blood, I am not a worm’… And like a universal wisdom was raining down on me I felt I understood true compassion, the power of love to destroy fear, the unity of all mankind, the meaning of giving, humility, strength and courage.

    Realizations ran through my mind, like dominos, knocking down one old thought pattern after another, releasing me from the mental prison I had found myself in. I laughed and cried wiggling my feet and toes as though I were a child again, rediscovering the joy of playfulness and the sensuality of my own body; and then came another realization; ‘I am not a victim, I have agency in this world.’

    I made my way down to the garden, outside the night sky was clear and the air was fresh. I smiled and laughed at the new feelings of love and appreciation I could feel. For my mum, my dad, all my family and friends; the night sky, the cool breeze, plants, slugs and everything else. Deepest of all I felt love for my sister, who has tried so hard to help me over the years. I felt the love and bond between us like a mixing of particles stretching across the universe, harmonious and inseparable. I bowed down again with appreciation and humility to whatever had released me. I was resurrected.

    The next day my depression was gone, I had no anxiety, I chatted with an old friend without an ounce of self-consciousness that would always have plagued me. And I felt like I am a man, not a boy for the first time in my life.

    I still am depression free am working everyday with gratitude and humility to build the kind of life I can be proud of.

    http://reset.me/personal-story/psilo...n-and-anxiety/


    Last edited by mr peabody; 18-10-2018 at 01:13.
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