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Substance Use Disorder

The association of psychedelic use and opioid use disorders among illicit users in the United States

February 14, 2017 / Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Background: Preliminary studies show psychedelic compounds administered with psychotherapy are potentially effective and durable substance misuse interventions. However, little is known about the association between psychedelic use and substance misuse in the general population. This study investigated the association between psychedelic use and past year opioid use disorders within illicit opioid users.

Methods: While controlling for socio-demographic covariates and the use of other substances, the relationship between classic psychedelic use and past year opioid use disorders was analyzed within 44,000 illicit opioid users who completed the National Survey on Drug Use and Health from 2008 to 2013.

Results: Among respondents with a history of illicit opioid use, psychedelic drug use is associated with 27% reduced risk of past year opioid dependence (weighted risk ratio = 0.73 (0.60–0.89) p = 0.002) and 40% reduced risk of past year opioid abuse (weighted risk ratio = 0.60 (0.41–0.86) p = 0.006). Other than marijuana use, which was associated with 55% reduced risk of past year opioid abuse (weighted risk ratio = 0.45 (0.30–0.66) p < 0.001), no other illicit drug was associated with reduced risk of past year opioid dependence or abuse.

Conclusion: Experience with psychedelic drugs is associated with decreased risk of opioid abuse and dependence. Conversely, other illicit drug use history is largely associated with increased risk of opioid abuse and dependence. These findings suggest that psychedelics are associated with positive psychological characteristics and are consistent with prior reports suggesting efficacy in treatment of substance use disorders.

Pisano, V. D., Putnam, N. P., Kramer, H. M., Franciotti, K. J., Halpern, J. H., & Holden, S. C. (2017). The association of psychedelic use and opioid use disorders among illicit users in the United States. Journal of Psychopharmacology, 0269881117691453.

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Ayahuasca: An ancient sacrament for treatment of contemporary psychiatric illness?

January 1, 2017 / Ayahuasca, Depressive Disorders, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Ayahuasca is a traditional psychoactive sacrament that’s been used in Amazonian shamanic rituals for hundreds of years. Ayahuasca is notorious for its psychedelic properties produced from the combination of monoamine oxidase inhibitors (MAOIs) found in the Banisteriopsis caapi vine and N-N-dimethyltryptamine from Psychotria viridis or Diplopterys cabrerana. Recently, ritual use of ayahuasca has increased and garnered attention for its potential in treating mental illnesses, such as substance use and depressive disorders. Due to its MAOI properties, there are serious drug interactions that may be of concern among patients who participate in ayahuasca use. The objectives of this paper are to describe ayahuasca’s pharmacology, potential drug interactions, and clinical data for its treatment potential in psychiatric illness.

Malcolm, B. J., & Lee, K. C. (2017). Ayahuasca: An ancient sacrament for treatment of contemporary psychiatric illness?. Mental Health Clinician, 7(1), 39-45. 10.9740/mhc.2017.01.039

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Clinical potential of psilocybin as a treatment for mental health conditions

January 1, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Psilocybin, a classic hallucinogen, is a chemical produced by more than 100 species of mushrooms worldwide. It has high affinity for several serotonin receptors, including 5-HT1A, 5-HT2A, and 5-HT2C, located in numerous areas of the brain, including the cerebral cortex and thalamus. With legislation introduced in 1992, more work is being done to further understand the implications of psilocybin use in a number of disease states. Certain mental health disease states and symptoms have been studied, including depressed mood, anxiety disorders, obsessive-compulsive disorder, alcohol use disorder, and tobacco use disorder. This article provides an in-depth review of the study design and results of psilocybin in each of these conditions and discusses the clinical potential for use.

Daniel, J., & Haberman, M. (2017). Clinical potential of psilocybin as a treatment for mental health conditions. Mental Health Clinician, 7(1), 24-28. 10.9740/mhc.2017.01.024

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

January 1, 2017 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Background: Substance use disorders are important contributors to the global burden of disease, but current treatments are not associated with high rates of recovery. The lack of approved and effective treatments is acutely problematic for psychostimulants like cocaine and crack cocaine. One promising alternative in the treatment of drug dependence in general and psychostimulants in particular is the use of the psychedelic alkaloid ibogaine combined with psychotherapy. This was recently shown to induce prolonged periods of abstinence in polydrug users, including psychostimulants. However, drug dependence treatments cannot be comprehensively evaluated with reductions in consumption alone, with current recommendations including secondary outcome measures like craving, family and social relationship, quality of life, and self-efficacy.

Methods: We therefore employed a directed approach to qualitative content analysis to evaluate the outcomes of a treatment combining ibogaine with cognitive-behavioral therapy based on data gathered from patient’s reports obtained in semi-structured interviews.

Main findings: The results revealed that patients benefited from the treatment in all the secondary outcomes, reporting decreases in craving and improvements in personal relationships, quality of life, and self-efficacy, thus supporting existing notions that treatments combining ibogaine and psychotherapy do have a therapeutic potential in the treatment of substance use disorders.

Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M., Chaves, B. D. R., Tófoli, L. F., & da Silveira, D. X. (2016). Treating drug dependence with the aid of ibogaine: A qualitative study. Journal of Psychedelic Studies, (0), 1-10. 10.1556/2054.01.2016.002

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Can 3,4,-methylenedioxymethamphetamine therapy be used to treat alcohol use disorder?

December 30, 2016 / MDMA, Papers, Psychology, Publications, Substance Use Disorder / By /

Abstract

Treating people with alcohol use disorder has been an important target area for psychedelic research – both in the first studies of the 1950s and during the Psychedelic Renaissance of the last 10 years. To date, most studies have looked at the classical psychedelic drugs as adjuncts to psychotherapy; with attention paid to the psychospiritual aspect of the experience as a central therapeutic process in effecting abstinence from drinking. Psychotherapy assisted with 3,4,-methylenedioxymethamphetamine (MDMA) has never been explored for treating alcohol use disorder. However, MDMA has some unique pharmacological characteristics – particularly its capacity for reducing the fear response and facilitating engagement in therapy around past psychological trauma – that could make it a useful candidate for tackling the core features of alcohol use disorder. This paper briefly describes the burden of alcohol use disorders and the history of psychedelic-assisted psychotherapy in the field of addictions. It gives the theoretical and experimental justification for MDMA-assisted psychotherapy for treating people with alcohol use disorder and introduces a forthcoming study from Bristol and London, UK, exploring the role for MDMA in treating a person with this challenging condition.

Sessa, B. (2016). Can 3, 4,-methylenedioxymethamphetamine therapy be used to treat alcohol use disorder?. Journal of Psychedelic Studies, (0), 1-9. 10.1556/2054.01.2016.003
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The antiaddictive effects of ibogaine: A systematic literature review of human studies

December 20, 2016 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Background and aims: Ibogaine is a naturally occurring hallucinogenic alkaloid with a therapeutic potential for reducing drug craving and withdrawal. To the best of our knowledge, no systematic review was previously performed assessing these effects. Thus, we conducted a systematic literature review of human studies assessing the antiaddictive effects of ibogaine.

Methods: Papers published up to July 2, 2016 were included from PubMed, LILACS, and SciELO databases following a comprehensive search strategy and a pre-determined set of criteria for article selection.

Results: Two hundred and fifty-nine studies were identified, of which eight met the established criteria. Seven studies were open-label case series with ibogaine and one study was a randomized, placebo-controlled clinical trial with noribogaine. Case series suggest that a single dose or a few treatments with ibogaine may significantly reduce drug withdrawal, craving, and self-administration in dependent individuals lasting from 24 h to weeks or months. No significant effects of noribogaine on opiate/opioid withdrawal were observed in the clinical trial.

Conclusions: Considering the necessity of new drugs that may produce fast-acting and sustained effects in opiate/opioid and cocaine dependence, the potential beneficial effects of ibogaine/noribogaine should be further investigated in controlled trials.

dos Santos, R. G., Bouso, J. C., & Hallak, J. E. (2016). The antiaddictive effects of ibogaine: A systematic literature review of human studies. Journal of Psychedelic Studies, (0), 1-9. 10.1556/2054.01.2016.001

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A One-Dose Psychedelic Fix for Addiction?

December 8, 2016 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By /

Abstract

A drug that mimics ibogaine, a hallucinogen used underground for decades as an antiaddiction agent, is now being tested in clinical trials

The psychedelic drug ibogaine is known for two things: its reputation in some circles as a panacea for addiction and the visceral hallucinations it induces. Positive anecdotes abound from people who have sought out the illegal drug at underground clinics.

Jacobson, R. (2017). A One-Dose Psychedelic Fix for Addiction?. Scientific American Mind, 28(1), 10-11. 10.1038/scientificamericanmind0117-10

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Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration

December 2, 2016 / MDMA, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Animal models of drug self-administration are currently the gold standard for making predictions regarding the relative likelihood that a recreational drug substance will lead to continued use and addiction. Such models have been found to have high predictive accuracy and discriminative validity for a number of drug classes including ethanol, nicotine, opioids, and psychostimulants such as cocaine and methamphetamine. Members of the entactogen class of psychostimulants (drugs that produce an “open mind state” including feelings of interpersonal closeness, intimacy and empathy) have been less frequently studied in self-administration models. The prototypical entactogen 3,4-methylenedioxymethamphetamine (MDMA; “Ecstasy”) supports self-administration but not with the same consistency nor with the same efficacy as structurally related drugs amphetamine or methamphetamine. Consistent with these observations, MDMA use is more episodic in the majority of those who use it frequently. Nevertheless, substantial numbers of MDMA users will meet the criteria for substance dependence at some point in their use history. This review examines the currently available evidence from rodent self-administration studies of MDMA and two of the new and emerging psychoactive substances (NPS) that produce entactogen type neuropharmacological responses – mephedrone (4-methylmethcathinone; 4MMC; “meow meow”) and methylone (3,4-methylenedioxymethcathinone). Overall, the current evidence predicts that these NPS entactogens have enhanced abuse liability compared with MDMA.

Aarde, S. M., & Taffe, M. A. (2016). Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration. 10.1007/7854_2016_54
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Biosynthesis of the psychotropic plant diterpene salvinorin A: Discovery and characterization of the Salvia divinorum clerodienyl diphosphate synthase

November 19, 2016 / Neuroscience, Papers, Pharmacology & Chemistry, Publications, Salvia / Salvinorin A, Substance Use Disorder / By / , , , , , ,

Abstract

Salvia divinorum commonly known as diviner’s sage, is an ethnomedicinal plant of the mint family (Lamiaceae). S. divinorum is rich in clerodane-type diterpenoids, which accumulate predominantly in leaf glandular trichomes. The main bioactive metabolite, salvinorin A, is the first non-nitrogenous natural compound known to function as an opioid-receptor agonist, and is undergoing clinical trials for potential use in treating neuropsychiatric diseases and drug addictions. We report here the discovery and functional characterization of two S. divinorumditerpene synthases (diTPSs), the ent-copalyl diphosphate (ent-CPP) synthase SdCPS1, and the clerodienyl diphosphate (CLPP) synthase SdCPS2. Mining of leaf- and trichome-specific transcriptomes revealed five diTPSs, two of which are class II diTPSs (SdCPS1-2) and three are class I enzymes (SdKSL1-3). Of the class II diTPSs, transient expression in Nicotiana benthamianaidentified SdCPS1 as an ent-CPP synthase, which is prevalent in roots and, together with SdKSL1, exhibits a possible dual role in general and specialized metabolism. In vivo co-expression and in vitro assays combined with NMR analysis identified SdCPS2 as a CLPP synthase. A role of SdCPS2 in catalyzing the committed step in salvinorin A biosynthesis is supported by its biochemical function, trichome-specific expression and absence of additional class II diTPSs in S. divinorum. Structure-guided mutagenesis revealed four catalytic residues that enabled the re-programming of SdCPS2 activity to afford four distinct products, thus advancing our understanding of how neo-functionalization events have shaped the array of different class II diTPS functions in plants, and may promote synthetic biology platforms for a broader spectrum of diterpenoid bioproducts.

Pelot, K. A., Mitchell, R., Kwon, M., Hagelthorn, D. M., Wardman, J. F., Chiang, A., … & Zerbe, P. (2016). Biosynthesis of the psychotropic plant diterpene salvinorin A: Discovery and characterization of the Salvia divinorum clerodienyl diphosphate synthase. The Plant Journal. 10.1111/tpj.13427
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The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens

November 15, 2016 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Classic hallucinogens share pharmacology as serotonin 5-HT2A, 5-HT2B, and 5-HT2Creceptor agonists. Unique among most other Schedule 1 drugs, they are generally non-addictive and can be effective tools in the treatment of addiction. Mechanisms underlying these attributes are largely unknown. However, many preclinical studies show that 5-HT2C agonists counteract the addictive effects of drugs from several classes, suggesting this pharmacological property of classic hallucinogens may be significant. Drawing from a comprehensive analysis of preclinical behavior, neuroanatomy, and neurochemistry studies, this review builds rationale for this hypothesis, and also proposes a testable, neurobiological framework. 5-HT2C agonists work, in part, by modulating dopamine neuron activity in the ventral tegmental area—nucleus accumbens (NAc) reward pathway. We argue that activation of 5-HT2Creceptors on NAc shell, GABAergic, medium spiny neurons inhibits potassium Kv1.x channels, thereby enhancing inhibitory activity via intrinsic mechanisms. Together with experiments that show that addictive drugs, such as cocaine, potentiate Kv1.x channels, thereby suppressing NAc shell GABAergic activity, this hypothesis provides a mechanism by which classic hallucinogen-mediated stimulation of 5-HT2C receptors could thwart addiction. It also provides a potential reason for the non-addictive nature of classic hallucinogens.

Canal, C. E., & Murnane, K. S. (2016). The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens. Journal of Psychopharmacology, 0269881116677104.
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