OPEN Foundation

Addiction

Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and Ayahuasca

Abstract

Substances known as psychedelics, hallucinogens and entheogens have been employed in ethnomedical traditions for thousands of years, but after promising uses in the 1950’s and 1960’s they were largely prohibited in medical treatment and human research starting in the 1970’s as part of the fallout from the war on drugs. Nonetheless, there are a number of studies which suggest that these substances have potential applications in the treatment of addictions. While these substances are generally classified as Schedule I, alleging no established medical uses and a high drug abuse potential, there is nonetheless evidence indicating they might be safe and effective tools for short term interventions in addictions treatment. Evidence suggests that the psychedelics have a much greater safety profile than the major addictive drugs, having extremely low levels of mortality, and producing little if any physical dependence. This paper reviews studies evaluating the use of LSD, peyote, ibogaine and ayahuasca in the treatment of dependencies and the possible mechanisms underlying the indications of effectiveness. Evidence suggests that these substances help assist recovery from drug dependency through a variety of therapeutic mechanisms, including a notable “after-glow” effect that in part reflects their action on the serotonin neurotransmitter system. Serotonin has been long recognized as central to the psychedelics’ well-known phenomenological, physical, emotional and cognitive dynamics. These serotonin-based dynamics are directly relevant to treatment of addiction because of depressed serotonin levels found in addict populations, as well as the role of serotonin as a neuromodulators affecting many other neurotransmitter systems.

Winkelman, M. (2015). Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and Ayahuasca. Current Drug Abuse Reviews, 7(2), 101-116. https://dx.doi.org/10.2174/1874473708666150107120011

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Salvinorin A and Related Compounds as Therapeutic Drugs for Psychostimulant-Related Disorders

Abstract

Pharmacological treatments are available for alcohol, nicotine, and opioid dependence, and several drugs for cannabis-related disorders are currently under investigation. On the other hand, psychostimulant abuse and dependence lacks pharmacological treatment. Mesolimbic dopaminergic neurons mediate the motivation to use drugs and drug-induced euphoria, and psychostimulants (cocaine, amphetamine, and methamphetamine) produce their effects in these neurons, which may be modulated by the opioid system. Salvinorin A is a κ-opioid receptor agonist extracted from Salvia divinorum, a hallucinogenic plant used in magico-ritual contexts by Mazateca Indians in México. Salvinorin A and its analogues have demonstrated anti-addiction effects in animal models using psychostimulants by attenuating dopamine release, sensitization, and other neurochemical and behavioral alterations associated with acute and prolonged administration of these drugs. The objective of the present article is to present an overview of the preclinical evidence suggesting anti-addictive effects of salvinorin A and its analogues.

dos Santos, R. G., Crippa, J. A., Machado-de-Sousa, J. P., & Hallak, J. E. (2015). Salvinorin A and Related Compounds as Therapeutic Drugs for Psychostimulant-Related Disorders. Current Drug Abuse Reviews, 7(2), 128-132. https://dx.doi.org/10.2174/1874473708666150107122741

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Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study

Abstract

Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants’ responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5–8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.

Bogenschutz, M. P., Forcehimes, A. A, Pommy, J. A., Wilcox, C. E., Barbosa, P. C. R., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114565144

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Can psychedelic compounds play a part in drug dependence therapy?

Abstract

After a 40-year hiatus there is now a revisiting of psychedelic drug therapy throughout psychiatry, with studies examining the drugs psilocybin, ketamine, ibogaine and ayahuasca in the treatment of drug dependence. Limitations to these therapies are both clinical and legal, but the possibility of improving outcomes for patients with substance dependency imposes an obligation to research this area.

Sessa, B., & Johnson, M. W. (2015). Can psychedelic compounds play a part in drug dependence therapy? The British Journal of Psychiatry, 206, 1-3. https://dx.doi.org/10.1192/bjp.bp.114.148031

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Psychedelic-facilitated smoking cessation: An online survey

Abstract

Aims:
Pilot laboratory results suggest psilocybin may be an efficacious adjunct to smoking cessation treatment. However, no study has examined smoking cessation after psychedelic use in naturalistic settings.
Methods:
We are conducting an online survey collecting demographics, smoking history, and other data from people who self-report quitting/reducing smoking after taking a psychedelic.
Results:
Among current completers (N=164), LSD (49%) and psilocybin (32%) were the drugs most commonly associated with quitting/reducing, with a mode of 2-5 lifetime uses each. Participants reported smoking a mean of 12 cigs/day for a mean of 8 yrs before the experience. 62(38%) reported total and continuing abstinence after their experience, with 29 of the 62 (47%) reporting >1yr abstinence, and 7 (11%) reporting >10 yrs abstinence. Another 67 of the 164 (41%) reported persisting smoking reduction, from a mode of 10-20 cigs/day before, to a mode of <1 cig/month after the experience. The remaining 35 (21%) reported temporary reduction, with 6 of the 35 (17%) reporting >1 yr reduction. Although the majority of withdrawal symptoms were rated as equal in severity to previous quit attempts, depression, irritability, anxiety, and craving were rated as “much less severe.” 141 of the 164 (86%) reported no premeditated intention to quit/reduce smoking, and 159 (97%) described their experience as highly meaningful, with
97 (59%) considering it among the 10 most meaningful experiences of their lives. Participants cited changed life priorities/values (26%), strengthened belief in their ability to quit (26%), and changed future orientation (17%) as the most important effects leading to quitting/reducing. Other changes reported after psychedelic use included reduced alcohol (38%) and other drug use (23%).
Conclusions:
Psychedelics may prompt temporary or prolonged smoking cessation, suggesting that careful administration in a treatment context may enhance motivation in changing addictive behaviors. Psychological and neurobiological mechanisms underlying such behavioral changes require further investigation.

Garcia-Romeu, A. P., Griffiths, R. R., & Johnson, M. W. (2015). Psychedelic-facilitated smoking cessation: An online survey. Drug and Alcohol Dependence, (146), e120. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.245
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Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues

Abstract

The neoclerodane diterpene salvinorin A, found in the leaves of Salvia divinorum, is a potent κ-opioid receptor agonist, making it an attractive scaffold for development into a treatment for substance abuse. Although several successful semisynthetic studies have been performed to elucidate structure-activity relationships, the lack of analogues with substitutions to the furan ring of salvinorin A has prevented a thorough understanding of its role in binding to the κ-opioid receptor. Herein we report the synthesis of several salvinorin A derivatives with modified furan rings. Evaluation of these compounds in a functional assay indicated that sterically less demanding substitutions are preferred, suggesting the furan ring is bound in a congested portion of the binding pocket. The most potent of the analogues successfully reduced drug-seeking behavior in an animal model of drug-relapse without producing the sedation observed with other κ-opioid agonists.

Riley, A. P., Groer, C. E., Young, D., Ewald, A. W., Kivell, B. M., & Prisinzano, T. E. (2014). Synthesis and Kappa Opioid Receptor Activity of Furan-Substituted Salvinorin A Analogues. Journal of medicinal chemistry. https://dx.doi.org/10.1021/jm501521d
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Ibogaine: useful in treating addiction to non-opioids?

iboga508It has been known for some time that ibogaine can probably help in the treatment of drug addiction. But up until now researchers focused primarily on the addiction to opioids like heroin and morphine. A group of scientists in Brazil found out that ibogaine might also help against addiction to alcohol, cannabis and cocaine, implying a wider range of potential therapeutic applications.

Treating drug dependence can be hard. Conventional therapies often are lengthy and costly. Nowadays the increased interest in the potential of psychedelics in the battle against addiction has urged new investigations. Several studies on the use of LSD and psilocybin for this purpose have been published [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][1]. Ibogaine is another psychedelic that has gained the attention of scientists. This is an alkaloid that can be found in the root bark of the Tabernanthe iboga plant, growing in West central Africa. As early as 1962 the substance was used in trials to overcome heroin addiction. But further investigation was made difficult by a statutory ban in many countries. In Brazil however, ibogaine is not an illegal substance, allowing research to continue. A group of scientists from the University of São Paulo, led by Eduardo Schenberg, retrospectively evaluated data from a private clinic in Curitiba, which treated patients with pure ibogaine HCl in a professional environment and as part of a larger psychotherapeutic program [2]. The patients in the study were addicts to alcohol, cannabis, cocaine, and/or crack cocaine. The researchers concluded that 61% of these patients were still abstinent after five to eight months, and that none of them experienced long-lasting negative side effects. Repeated sessions (two or three times) appeared to be especially effective.

Using ibogaine in the treatment of drug addiction is not without risks however. The substance can cause serious arrhythmia, which has led to several fatalities in the past. But according to Schenberg et al., most of these cases were probably due to a pre-existing heart disorder (e.g. “long-QT-syndrome”, a condition causing severe irregular heartbeat). Moreover, the ibogaine or iboga extracts in those cases were often used without quality control and without the supervision of trained and qualified medical staff. Using other psychoactive substances and certain prescription drugs shortly before the ibogaine ingestion can also cause adverse effects. For that reason, the clinic in which this study took place implemented a protocol to ensure that patients are abstinent at least thirty days before the ibogaine is administered. If this is observed and sessions are accompanied in a professional way, then ibogaine can probably be a good aid in the treatment of addiction, according to the researchers. They admit however that more research is necessary, also into the potential adverse effects of ibogaine on the heart.


 
[1] Johnson et al. (2014) and Krebs & Johansen (2012)
[2] Schenberg et al. (2014)
 
References

Schenberg, E. E., de Castro Comis, M. A., Rasmussen Chaves, B. & da Silveira, D. X. (2014). Treating drug dependence with the aid of ibogaine: A retrospective study. Journal of Psychopharmacology, 28(11), 993-1000. [Abstract]
Krebs, T. S. & Johansen, P. Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 26(11), 994-1002. [Abstract]
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology, 28(11), 983-992. [Abstract][/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Treating drug dependence with the aid of ibogaine: A retrospective study

Abstract

Ibogaine is an alkaloid purported to be an effective drug dependence treatment. However, its efficacy has been hard to evaluate, partly because it is illegal in some countries. In such places, treatments are conducted in underground settings where fatalities have occurred. In Brazil ibogaine is unregulated and a combined approach of psychotherapy and ibogaine is being practiced to treat addiction. To evaluate the safety and efficacy of ibogaine, we conducted a retrospective analysis of data from 75 previous alcohol, cannabis, cocaine and crack users (72% poly-drug users). We observed no serious adverse reactions or fatalities, and found 61% of participants abstinent. Participants treated with ibogaine only once reported abstinence for a median of 5.5 months and those treated multiple times for a median of 8.4 months. This increase was statistically significant (p < 0.001), and both single or multiple treatments led to longer abstinence periods than before the first ibogaine session (p < 0.001). These results suggest that the use of ibogaine supervised by a physician and accompanied by psychotherapy can facilitate prolonged periods of abstinence, without the occurrence of fatalities or complications. These results suggest that ibogaine can be a safe and effective treatment for dependence on stimulant and other non-opiate drugs.

Schenberg, E.E., de Castro Comis, M.A., Rasmussen Chaves, B. & da Silveira, D. X. (2014). Treating drug dependence with the aid of ibogaine: A retrospective study. Journal of Psychopharmacology, 28(11), 993-1000. http://dx.doi.org/10.1177/0269881114552713
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Back to the future: A return to psychedelic treatment models for addiction

Abstract

The discovery of the 5HT2aR agonist hallucinogen (i.e. classic psychedelic) lysergic acid diethylamide (LSD) by Albert Hofmann in 1943 was a global watershed event. Not only did it spark wide interest in the nature of consciousness and the role of neurotransmission in brain function, it opened new avenues of potential treatment for a range of mental health conditions (Hofmann, 2013). The scientific community of the 1950s through the early 1970s responded to Hofmann’s discovery by producing more than 1000 manuscripts describing the treatment of 40,000 patients (Nutt et al., 2013). Despite promising if not remarkable indications of efficacy (Krebs and Johansen, 2012; Savage and McCabe, 1973),sensationalized reports of recreational LSD use prompted legal restrictions that ultimately rendered research with LSD and …

Hendricks, P. S. (2014). Back to the future: A return to psychedelic treatment models for addiction. Journal of Psychopharmacology, 28(11), 981-982. http://dx.doi.org/10.1177/0269881114550935
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Psilocybin against tobacco addiction

A positive treatment perspective for one of the current most persistent and deadliest addictions comes from a psilocybin-assisted smoking cessation study carried out at the Johns Hopkins University School of Medicine in Maryland, USA [2].

The form of treatment consisted of up to three psilocybin sessions additional to cognitive behavioral therapy. Twelve out of fifteen participants (80%) succeeded in quitting their habit after this treatment for a minimum of six months [3]. Participants experienced an increased faith to effectively deal with the addiction, a heightened spiritual awareness and an uplifted state of overall well-being. An interesting finding was that, although three participants didn’t succeed in quitting, this group turned out smoking less cigarettes a day six months after the beginning of the treatment.

Because of the study design lacking a control group, it is not (yet) possible to solely ascribe the therapeutic effect of the treatment to the characteristics of psilocybin. Nevertheless, these results promise a better treatment perspective for psilocybin combined with cognitive behavioral therapy than for regular treatment options. The success rate in this study being 80%, compared to 25% to 34% when treated with buproprion or varenicline respectively [4], or compared to around 50% when treated with a combination of bupropion, nicotine replacement, and intensive cognitive behavioral therapy [5][6]. More scientific studies would be necessary in order to understand the full potential of treating smoking addiction with psilocybin or other pharmacons that have their mechanism of action on the 5-HT2A-receptor.

The idea of using psychedelics to fight addiction is nothing new. In the 50s and 60s there were a lot of research projects focusing on the therapeutic potential of these compounds. The interested reader might want to take a look at a meta-analysis by Teri Krebs (2012), which, based on six of these studies, concluded that the treatment of alcoholism using LSD seemed to be very effective.


[1] World Health Organization (2011)
[2] Johnson, Garcia-Romeu, Cosimano, & Griffiths (2014)
[3] The notion should be considered that several participants indicated to have a relapse period between the last psilocybin session and six month follow-up, but that they were able to correct it themselves and continued as non-smokers until follow-up.
[4] Gonzales et al., 2014; Jorenby et al., 2014
[5] Hall et al., 2009; Killen et al., 2008
[6] Success rates are based on 7 day point prevalence abstinence measures of smoking behavior. Gathered by self-report and urine- and breath analyzes.

References
Gonzales, D., Rennard, S. I., Nides, M., Oncken, C., Azoulay, S., Billing, C. B., … Reeves, K. R. (2014). Varenicline, an ␣ 4 ␤ 2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Sustained-Release Bupropion and Placebo for Smoking Cessation, 296(1), 47–55.
Hall, S. M., Humfleet, G. L., Muñoz, R. F., et al. (2009). Extended treatment of older cigarette smokers. Addiction, 104, 1043-1052
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology (Oxford, England), (September). doi:10.1177/0269881114548296
Jorenby, D. E., Hays, J. T., Rigotti, N. A., Azoulay, S., Watsky, E. J., Williams, K. E., … Reeves, K. R. (2014). Efficacy of Varenicline, an α4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Placebo or Sustained-Release Bupropion for Smoking CessationA Randomized Controlled Trial. JAMA, 296, 56-63.
Killen, J. D., Fortmann, S. P., Schatzberg, A. F., et al. (2008). Extended cognitive behavior therapy for cigarette smoking cessation. Addiction, 103, 1381-1390.
Krebs, T. S., & Johansen, P.-Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology (Oxford, England), 26(7), 994–1002. doi:10.1177/0269881112439253[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

22 May - Delivering Effective Psychedelic Clinical Trials

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