Pharmacological options in the treatment of addiction

[MeDieViL]

Shifting dopaminergic balance to brainarea's mostly involved in motivation rather then the nucleus accumbens should counteract the problem of getting to lazy on amp, and make us productive.

 

[MeDieViL]

i'm using naltrexone to try to stay off alcohol.. from your research, if i am to take 50mg everyday or just when i feel the urge to drink, could it help me?

Yes, but if you feel the urge for drink you may actually just drink instead of taking the naltrexone, so better to stay on it chronically.

 

[MeDieViL]

wesley have you tried the naltrexone and amphetamine combo yet? i want to kno how it works out.


i too have the same problem. amphetamines give me excessive euphoria without much motivation. prob related to excessive mesolimbic stimulants are less mesocortical.

I want to try this combo soon.

 

[MeDieViL]

Il add a few reviews looking at several receptorsystems in the brain and how they modulate drug addiction.

CNS Drugs. 2009 Nov 1;23(11):939-52. doi: 10.2165/11310920-000000000-00000.
Cholinergic functioning in stimulant addiction: implications for medications development.
Sofuoglu M, Mooney M.

Yale University, School of Medicine, Department of Psychiatry and VA Connecticut Healthcare System, West Haven, Connecticut 06516, USA. [email protected]
Abstract
Acetylcholine, the first neurotransmitter discovered, participates in many CNS functions, including sensory and motor processing, sleep, nociception, mood, stress response, attention, arousal, memory, motivation and reward. These diverse cholinergic effects are mediated by nicotinic- and muscarinic-type cholinergic receptors (nAChR and mAChR, respectively). The goal of this review is to synthesize a growing literature that supports the potential role of acetylcholine as a treatment target for stimulant addiction. Acetylcholine interacts with the dopaminergic reward system in the ventral tegmental area, nucleus accumbens and prefrontal cortex. In the ventral tegmental area, both nAChR and mAChR stimulate the dopaminergic system. In the nucleus accumbens, cholinergic interneurons integrate cortical and subcortical information related to reward. In the prefrontal cortex, the cholinergic system contributes to the cognitive aspects of addiction. Preclinical studies support a facilitative role of nicotinic receptor agonists in the development of stimulant addiction. In contrast, nonselective muscarinic receptor agonists seem to have an inhibitory role. In human studies, acetylcholinesterase inhibitors, which increase synaptic acetylcholine levels, have shown promise for the treatment of stimulant addiction. Further studies testing the efficacy of cholinergic medications for stimulant addiction are warranted.

Acta Pharmacol Sin. 2010 Sep;31(9):1065-70. Epub 2010 Aug 23.
The role of kappa-opioid receptor activation in mediating antinociception and addiction.
Wang YH, Sun JF, Tao YM, Chi ZQ, Liu JG.

Nanjing University of Chinese Medicine, China.
Abstract
The kappa-opioid receptor (KOR), a member of the opioid receptor family, is widely expressed in the central nervous system and peripheral tissues. Substantial evidence has shown that activation of KOR by agonists and endogenous opioid peptides in vivo may produce a strong analgesic effect that is free from the abuse potential and the adverse side effects of mu-opioid receptor (MOR) agonists, such as morphine. In addition, activation of the KOR has also been shown to exert an inverse effect on morphine-induced adverse actions, such as tolerance, reward, and impairment of learning and memory. Therefore, the KOR has received much attention in the effort to develop alternative analgesics to MOR agonists and agents for the treatment of drug addiction. However, KOR agonists also produce several severe undesirable side effects such as dysphoria, water diuresis, salivation, emesis, and sedation in nonhuman primates, which may limit the clinical utility of KOR agonists for pain and drug abuse treatment. This article will review the role of KOR activation in mediating antinociception and addiction. The possible therapeutic application of kappa-agonists in the treatment of pain and drug addiction is also discussed.

Prog Neurobiol. 2010 Nov;92(3):421-41. Epub 2010 Jul 16.
Involvement of the brain histaminergic system in addiction and addiction-related behaviors: a comprehensive review with emphasis on the potential therapeutic use of histaminergic compounds in drug dependence.
Brabant C, Alleva L, Quertemont E, Tirelli E.

Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT 06508, USA. [email protected]
Abstract
Neurons that produce histamine are exclusively located in the tuberomamillary nucleus of the posterior hypothalamus and send widespread projections to almost all brain areas. Neuronal histamine is involved in many physiological and behavioral functions such as arousal, feeding behavior and learning. Although conflicting data have been published, several studies have also demonstrated a role of histamine in the psychomotor and rewarding effects of addictive drugs. Pharmacological and brain lesion experiments initially led to the proposition that the histaminergic system exerts an inhibitory influence on drug reward processes, opposed to that of the dopaminergic system. The purpose of this review is to summarize the relevant literature on this topic and to discuss whether the inhibitory function of histamine on drug reward is supported by current evidence from published results. Research conducted during the past decade demonstrated that the ability of many antihistaminic drugs to potentiate addiction-related behaviors essentially results from non-specific effects and does not constitute a valid argument in support of an inhibitory function of histamine on reward processes. The reviewed findings also indicate that histamine can either stimulate or inhibit the dopamine mesolimbic system through distinct neuronal mechanisms involving different histamine receptors. Finally, the hypothesis that the histaminergic system plays an inhibitory role on drug reward appears to be essentially supported by place conditioning studies that focused on morphine reward. The present review suggests that the development of drugs capable of activating the histaminergic system may offer promising therapeutic tools for the treatment of opioid dependence.

Pharmacol Res. 2007 Nov;56(5):418-27. Epub 2007 Sep 8.
Endocannabinoid regulation of relapse mechanisms.
Fattore L, Fadda P, Fratta W.

Institute of Neuroscience, CNR, National Research Council, Italy. [email protected]
Abstract
Addiction involves a complex neuropharmacologic behavioural cycle, in which positive reinforcement exerted by the drug and the negative state of withdrawal drive the user to extremes to obtain the drug. Comprehensive studies have established that relapse is the most common outcome of recovery programs treating addictive behaviours. Several types of anticraving medication are available nowadays, such as naltrexone for the treatment of alcoholism, bupropion for nicotine, methadone or buprenorphine for heroin. This review focuses on recent behavioural data providing a rationale for an endocannabinoid mechanism underlying reinstatement of compulsive drug seeking. Studies supporting the contention that reinstatement of extinguished drug self-administration behaviour may be generated by cannabinoid CB1 receptor agonists and attenuated, if not blocked, by CB1 receptor antagonists, are here reviewed. In support to these findings, conditioned place preference studies substantiate the involvement of the endocannabinoid system in recidivism mechanisms by demonstrating that motivation to relapse can be triggered by CB1 receptor activation while blockade of such receptors may prevent reinstatement of place conditioning induced by either drug primings or drug-associated cues. Finally, biochemical studies evaluating changes in endocannabinoid levels, CB1 receptor density and CB1 mRNA expression during re-exposure to drug following extinction are also examined. Taken together, the evidence available has important implications in the understanding and treatment of relapsing episodes in patients undergoing detoxification.

Neuropsychiatr Dis Treat. 2007 Dec;3(6):711-21.
Role of endocannabinoids in regulating drug dependence.
Parolaro D, Vigano D, Realini N, Rubino T.

Neuroscience Center, DBSF, University of Insubria, Busto Arsizio, Italy.
Abstract
This review will discuss the latest knowledge of how the endocannabinoid system might be involved in treating addiction to the most common illicit drugs. Experimental models are providing increasing evidence for the pharmacological management of endocannabinoid signaling not only to block the direct reinforcing effects of cannabis, opioids, nicotine and ethanol, but also for preventing relapse to the various drugs of abuse, including opioids, cocaine, nicotine, alcohol and metamphetamine. Preclinical and clinical studies suggest that the endocannabinoid system can be manipulated by the CB1 receptor antagonist SR141716A, that might constitute a new generation of compounds for treating addiction across different classes of abused drugs.

Still working on it, contributes with reviews looking at certain neurotransmitters with a collection of all data how they modulate addiction are apreciated.

 

[negrogesic]

Finding a compound that "reduces cravings" or the subjective desire to abuse a given compound (without acting as a substitute) is tricky. A normal human body should be capable of feeling "joy" without the use of exogenous compounds. Anhedonia induced by a so called "anti-addictive" compound is not an acceptable "trade-off" in my opinion.

The best treatment for cravings that are primarily "psychic" is non-pharmacological. Physical exercise is immensely powerful in this regard, and its benefits are not limited to opioid addicts. Engaging in things of interest....things capable of producing "joy" are also helpful (in my case, composing music, playing the piano, and particularly, conducting my original scores, brings this rare "joy"). Throwing drugs at drugs can and does "work", in my case, methadone was extremely effective, but it can also fail miserably. I think it is (in the end) pointless to chase after some "novel" compound or cocktail to magically "treat" addiction.......perhaps we will see some meaningful modulating of addictive behaviors in the future via gene therapy, but in the meantime.....

 

[MeDieViL]

There is no magic bullet, but many compounds have been shown to reduce craving for certain drugs in clinical trials, its definatly possible and its a help towards recovery.

While meds arent the magic bullets, getting heroin addicts interesting in biking around and playing piana isnt either.

They can all help no doubt about that, but combining them is the best option, and this thread was to discuss the pharmaceutical options.

The thread isnt about chasing a magic compound, but to discuss the current possibility's.

 

[MeDieViL]

Brain Res Brain Res Rev. 1993 Sep-Dec;18(3):247-91.
The neural basis of drug craving: an incentive-sensitization theory of addiction.
Robinson TE, Berridge KC.

Department of Psychology, University of Michigan, Ann Arbor 48104-1687.
Abstract
This paper presents a biopsychological theory of drug addiction, the 'Incentive-Sensitization Theory'. The theory addresses three fundamental questions. The first is: why do addicts crave drugs? That is, what is the psychological and neurobiological basis of drug craving? The second is: why does drug craving persist even after long periods of abstinence? The third is whether 'wanting' drugs (drug craving) is attributable to 'liking' drugs (to the subjective pleasurable effects of drugs)? The theory posits the following. (1) Addictive drugs share the ability to enhance mesotelencephalic dopamine neurotransmission. (2) One psychological function of this neural system is to attribute 'incentive salience' to the perception and mental representation of events associated with activation of the system. Incentive salience is a psychological process that transforms the perception of stimuli, imbuing them with salience, making them attractive, 'wanted', incentive stimuli. (3) In some individuals the repeated use of addictive drugs produces incremental neuroadaptations in this neural system, rendering it increasingly and perhaps permanently, hypersensitive ('sensitized') to drugs and drug-associated stimuli. The sensitization of dopamine systems is gated by associative learning, which causes excessive incentive salience to be attributed to the act of drug taking and to stimuli associated with drug taking. It is specifically the sensitization of incentive salience, therefore, that transforms ordinary 'wanting' into excessive drug craving. (4) It is further proposed that sensitization of the neural systems responsible for incentive salience ('for wanting') can occur independently of changes in neural systems that mediate the subjective pleasurable effects of drugs (drug 'liking') and of neural systems that mediate withdrawal. Thus, sensitization of incentive salience can produce addictive behavior (compulsive drug seeking and drug taking) even if the expectation of drug pleasure or the aversive properties of withdrawal are diminished and even in the face of strong disincentives, including the loss of reputation, job, home and family. We review evidence for this view of addiction and discuss its implications for understanding the psychology and neurobiology of addiction.

Could be an interesting paper.

Adv Pharmacol. 2010;58:373-96.
GABAB receptors in addiction and its treatment.
Tyacke RJ, Lingford-Hughes A, Reed LJ, Nutt DJ.

Neuropsychopharmacology Unit, Division of Experimental Medicine and Therapeutics, Imperial College London, London, UK.
Abstract
The GABA(B) receptor plays an important role in the control of neurotransmitter release, and experiments using preclinical models have shown that modulation of this receptor can have profound effects on the reward process. This ability to affect the reward process has led to clinical investigations into the possibility that this could be a viable target in the treatment of addiction. Presented here is an overview of a number of studies testing this hypothesis in different drug dependencies. The studies reviewed have used the GABA(B) receptor agonist baclofen, which is currently the only GABA(B) agonist for use in humans. In addition, studies using the non-specific GABA(B) receptor agonists vigabatrin and tiagabine have been included. In some of the studies these were found to have efficacy in the initiation and maintenance of abstinence, as an anti-craving treatment and alleviation of withdrawal syndromes, while in other studies showing limited effects. However, there is enough evidence to suggest that modulators of the GABA(B) receptor have potential as adjunct treatments to aid in the initiation of abstinence, maintenance of abstinence, and prevention of cue-related relapse in some addictions. This potential is at present poorly understood or studied and warrants further investigation.

CNS Drugs. 2009;23(5):361-7. doi: 10.2165/00023210-200923050-00001.
Complete suppression of craving in alcohol-dependent individuals: is it possible?
Kiefer F.

Department of Addictive Behaviour and Addiction Medicine, University of Heidelberg, Central Institute of Mental Health, Mannheim 68159, Germany. [email protected]
Abstract
A recent preliminary, single-case report suggested that baclofen not only reduces but may completely suppress craving in alcohol-dependent individuals. The current article summarizes the neurobiological basis of drug craving, and the pharmacological targets that have been shown to be involved in modulating such craving. The potential usefulness of agents that suppress craving is discussed. However, beyond individual case reports, no evidence is available to indicate that targeting a single neurobiological pathway will be sufficient to completely suppress craving in unselected individuals. Nevertheless, subgroups that carry specific characteristics associated with single receptor dysfunction might benefit from a targeted treatment. Further research is needed to enable clinicians to detect these subgroups.

CNS Drugs. 2007;21(8):693.
Baclofen as a craving-suppressing agent.
Ameisen O.

Comment on:

There's alot of data to look at, anyway i think its possible that with synergetic and well tought pharmaceutical support addiction can be beaten completely, wishfull thinking? Who knows, its all worth investigating.

 

[MeDieViL]

If sensitization is the first step in addiction, and we know with what agents we could inhibit that, then we allready have some massive advantages in the case of harm reduction, not saying its possible, but we need to look into this.

 

[Wizzle]

I tend to agree with negrogesic that reducing craving will be very tricky. When all other therapies fail, maintenence-therapy is the only option. Sometimes drugs of abuse are very effective at keeping mental disorders at bay, and I see no reason for putting someone on several different psych meds instead of methadone or heroin.

In my opinion should consist of:

- Agents that prevent tolerance from occuring
- Agent that atenuates withdrawals
- Agent that inhibits craving
- Substitution with a simular drug that isnt problematic in low daily doses, eventually combined with low dose naltrexone to atenuate its reinforcing effects.

Methadone does all of these things!

 

[23536]

I agree that methadone fits all those criteria, and does so very well. The problem remains, though, that one is still dependent on methadone. How does one become dependent on nothing should be a central question here.

Also, what is methadone comparable to in its value as an NMDA antagonist? Is it DXM-like, memantine-like or what?

 

[negrogesic]

Methadone should be prescribed in doses as high as the patient wants (making sure they are actually taking it via blood testing, peak and troughs, etc), monitoring resp rates etc. Basically, in cases of severe opioid addiction, the addict should be given large doses of methadone, in doses greater than those needed to reduce withdrawal symptoms, enough to induce narcosis. Some clinics impose an arbitrary ceiling of 180mg, which has no clinical basis. Basically, bump the dosage up 10mg a week. Eventually even the most severe addicts will get to a point where they decline further dose increase. When I got to 380mg, i had more than enough, and stayed on this dose until i realized "why in the hell am I taking 38 tablets of this"........basically I had enough.

Such a technique would provoke fear in many physicians, because of the issues regarding medico-legal liability (patients can and do OD on methadone, and families may sue for wrongful death) and due to fear of being sanctioned by the medical board for" overprescription" (this is an issue with the DEA, FDA and state regulatory agencies). Unfortunately, some 'ambitious' city/district prosecutors like to prosecute these cases due to their high profile, and in some cases, are looking to further their career (judicial appointment, etc).

Note: while complicated by a benzo addiction (I stopped benzos before the opioid), i have no chronic pain; my case was true opioid addiction not caused or linked to pain or some severe psychiatric trauma. Cases involving legitimate chronic are different.

 

[Wizzle]

I do not believe it is possible to become dependent on nothing without taking a long hard look at yourself. To believe that addiction can just dissappear with pharmacological intervention is wishful thinking.

I do believe pharms can help, but it stops there.

I'll have to get back at methadone's value as an nmda-antagonist. It is obviously effective enough to prevent tolerance.

 

[negrogesic]

Yes these are only tools. The real question is a reflective one. I do not like referring to addiction as a "disease".....it is a behavioral issue that virtually all humans (and primates!) possess. All human beings, in one way or another, are "reward seeking". Drug addiction is simply a manifestation of this inherent behavior, which yes, does appear to vary in degree as a result of many factors (genetics/comorbidities, situational/environmental etc etc).

Pharmacological agents for the treatment of these behaviors (with or without an attributable neuropsychiatric basis) that do not directly modulate or emulate the mechanism of said drug of abuse, lack CNS-activity, or have punitive properties (ex, disulfiram, forced naltrexone treatment). Sure there are compounds like Lobeline, but that compound has a whole host of issues.......

I am opposed to rapid detoxification under general anesthesia (having witnessed said procedures; they are brutal, disgusting, expensive, and often ineffective). They are also dangerous, and the long-term health effects from these procedures are unknown. But, they are very profitable, arguably more so than "inpatient rehab".

While I am an advocate of narcotic replacement therapy (even if it is buprenorphine, prescribed by inexperienced psychiatrists with no real understanding of opioid addiction), such an option generally NOT recommended for cocaine, methamphetamine etc. Under proper circumstances, an opioid addict can (with relative safety) be given as much of a substitutable opioid as so desired by the patient (intravenous opioid replacement therapy, while shown to be efficacious in some, intrinsically carries greater risks.....patients should 'generally' not be encouraged to self-inject, even with 'standardized' narcotics like DAM ampules). But the option for such treatment should be available, there is no "one size fits all" treatment, although suboxone has been marketed as such (it is actually a rather poor treatment for those with ultra-high dose dependencies or acute chronic pain issues). Interestingly, suboxone seems to be injected far more frequently than methadone, particularly when using methadone tablets. Suboxone is also prone to insufflation, a method that is almost never seen with methadone. Again, the bioavailability of methadone is very high and has more reliable pharmacokinetics. Levorphanol, though more potent, sedating and complex, is also highly bioavailable could potentially be used in narcotic replacement therapy. Generally, I don't like the ultra-potent oripavine derivatives, like dihydroetorphine (more potent than buprenorphine, and while apparently a pure agonist, it is somewhat mysterious).

 

[MeDieViL]

All human beings, in one way or another, are "reward seeking". Drug addiction is simply a manifestation of this inherent behavior

True, however its very clear drugs induce changes in the brain wich facilate or make you more prone to getting addicted to a certain drug.

 

[23536]

I do not believe it is possible to become dependent on nothing without taking a long hard look at yourself.

Psychedelics can help you look harder (so to speak). This is one of the principles behind iboga therapy.

 

[negrogesic]

I will admit i am naive as to the therapeutic value of ibogaine.................

 

[23536]

^not that you'll get to prescribe it in the foreseeable future

p.s. what's the consequence of a doctor prescribing buprenorphine without a DATA certification?

 

[OCitchy714]

But we would still need a part of the puzzle, the chasing for euphoria makes an addict lose intrest in other tasks, in case of amphetamine i beleive that is because balance is way to shifted to the nucleus accumbens, theoretically with naltrexone we can shift dopaminergic balance to more motivational structures, shifting balance away from the nucleus accumbens, ideal for people that want to be productive on amp instead of being lazy, check this experience:

So its possible to keep alot of the mood boost, therefor its a combination i would want to try, just not because i take too much amp, but because i take it for adhd but i still dont give a shit about things.

Well when i quit doing heroin around day 30 being sober starting to get the fog out of my head i decided to started to run everyday and the endorphin release made me feel great all day everyday life was really good intill I got a really bad form of staph. that infected my left knee it was quite severe i was in the hospital for about month and i had 3 operations done on my knee to remove the abcesse and get rid of the cellulitis. of course i could not do all this with out my DOC opiates to help with the terrible pain i was suffering, and From that I'am back to square one I eventually ran out of my scripts and started banging heroin again or anything that will keep me from W'D I'am stuck in this cycle of pleasant hell btw i was sober for 4 months intill i got my infection 3 months in rehab that really helped and 1 month on my own then boom god pissed all over me and said "no your not done getting high" I just started subs a couple days ago and I'am going back to rehab for another three months in a few days

 

[Deleted member 137730]

i think the most potent anti addiction medication is abilify in high doses. It has a huge half life of up to 146 hours and is active a MINUTE doses. You cant get high at all on the following:

all stimulants
opiates
psychadelics
alcohol

EVERYTHING REALLY.


I AM IN HELL ON THIS MEDICATION

 

[MeDieViL]

i think the most potent anti addiction medication is abilify in high doses. It has a huge half life of up to 146 hours and is active a MINUTE doses. You cant get high at all on the following:

all stimulants
opiates
psychadelics
alcohol

EVERYTHING REALLY.


I AM IN HELL ON THIS MEDICATION

Medication that blocks a high is the most retarded treatment of addiction imo, it would make me take massive doses of stuff to the point of killing me.