Current Drug Abuse Reviews - Volume 6, Issue 1, 2013

Ibogaine is a psychoactive alkaloid derived from Tabernanthe iboga, a plant used in initiatory rituals in West Central Africa. Largely because of ibogaine’s status as a Schedule I substance in the U.S., the development of ibogaine’s use in the treatment of drug addiction took place outside conventional clinical and medical settings. This article reviews the history of ibogaine’s use in the treatment of drug addiction, and discusses progress made towards, and obstacles blocking, the establishment of controlled clinical trials of ibogaine’s efficacy. Preclinical research has generally supported anecdotal claims that ibogaine attenuates withdrawal symptoms and reduces drug cravings. Concerns about ibogaine’s safety, as well as a dearth of solid data from human studies, have hampered progress in its development as an approved medication. This article outlines major findings from preclinical studies, discusses concerns about ibogaine’s safety, and details previous and ongoing research on ibogaine’s use as an anti-addictive treatment for humans.

Recent developments in the study of classic hallucinogens, combined with a re-appraisal of the older literature, have led to a renewal of interest in possible therapeutic applications for these drugs, notably their application in the treatment of addictions. This article will first provide a brief review of the research literature providing direct and indirect support for the possible therapeutic effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of addictions. Having provided a rationale for clinical investigation in this area, we discuss design issues in clinical trials using classic hallucinogens, some of which are unique to this class of drug. We then discuss the current status of this field of research and design considerations in future randomized trials.

Introduction: This paper reports results from a preliminary observational study of ayahuasca-assisted treatment for problematic substance use and stress delivered in a rural First Nations community in British Columbia, Canada. Methods: The “Working with Addiction and Stress” retreats combined four days of group counselling with two expert-led ayahuasca ceremonies. This study collected pre-treatment and six months follow-up data from 12 participants on several psychological and behavioral factors related to problematic substance use, and qualitative data assessing the personal experiences of the participants six months after the retreat. Findings: Statistically significant (p < 0.05) improvements were demonstrated for scales assessing hopefulness, empowerment, mindfulness, and quality of life meaning and outlook subscales. Self-reported alcohol, tobacco and cocaine use declined, although cannabis and opiate use did not; reported reductions in problematic cocaine use were statistically significant. All study participants reported positive and lasting changes from participating in the retreats. Conclusions: This form of ayahuasca-assisted therapy appears to be associated with statistically significant improvements in several factors related to problematic substance use among a rural aboriginal population. These findings suggest participants may have experienced positive psychological and behavioral changes in response to this therapeutic approach, and that more rigorous research of ayahuasca-assisted therapy for problematic substance use is warranted.

The multidisciplinary research on Salvia divinorum and its chemical principles is analyzed concerning whether the ethnobotany, phytochemistry, mental effects, and neuropharmacology of this sacred psychoactive plant and main principle clarify its experienced effects and divinatory uses. The scientific pursuit spans from the traditional practices, continues with the botanical identification, isolation of active molecules, characterization of mental and neural effects, possible therapeutic applications, and impinges upon the mind-body problem. The departure point is ethnopharmacology and therefore the traditional beliefs, ritual uses, and mental effects of this Mazatec sacred mint recorded during a 1973- 1983 field research project are described. A water potion of crushed leaves produced short-lasting light-headedness, dysphoria, tactile and proprioceptive sensations, a sense of depersonalization, amplified sound perception, and an increase visual and auditory imagery, but not actual hallucinations. Similar effects were described using questionnaires and are attributable to salvinorin A, but cannot be explained solely by its specific and potent brain kappa-opioid receptor agonist activity. Some requirements for a feasible classification and mechanism of action of consciousness-altering products are proposed and include the activation of neural networks comprising several neurochemical systems. Top-down analyses should be undertaken in order to characterize such neural networks and eventually allowing to explore the differential ethnic effects. As is the case for other consciousness-altering preparations, a careful and encompassing research on this plant and principle can be consequential to endeavors ranging from the mind-body problem, a better understanding of shamanic ecstasy, to the potential generation of analgesic, antidepressant, and drug-abuse attenuating products.

A wider array of treatments are needed for people with substance abuse disorders. Some psychedelic compounds have been assessed as potential substance abuse treatments with promising results. MDMA may also help treat substance abuse based on shared features with psychedelic compounds and recent reports indicating that MDMAassisted psychotherapy can reduce symptoms of PTSD. Narrative reports and data from early investigations found that some people reduced or eliminated their substance use after receiving MDMA, especially in a therapeutic setting. MDMA is a potent monoamine releaser with sympathomimetic effects that may indirectly activate 5-HT2A receptors. It increases interpersonal closeness and prosocial feelings, potentially through oxytocin release. Findings suggest that ecstasy, material represented as containing MDMA, is associated with deleterious long-term effects after heavy lifetime use, including fewer serotonin transporter sites and impaired verbal memory. Animal and human studies demonstrate moderate abuse liability for MDMA, and this effect may be of most concern to those treating substance abuse disorders. However, subjects who received MDMA-assisted psychotherapy in two recent clinical studies were not motivated to seek out ecstasy, and tested negative in random drug tests during follow-up in one study. MDMA could either directly treat neuropharmacological abnormalities associated with addiction, or it could indirectly assist with the therapeutic process or reduce symptoms of comorbid psychiatric conditions, providing a greater opportunity to address problematic substance use. Studies directly testing MDMA-assisted psychotherapy in people with active substance abuse disorder may be warranted.

Opioid maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Risk of diversion and toxicity of opioid prescription drugs, including buprenorphine, causes significant concerns. This is particularly the case in the United States, where the number of related emergency visits is increasing, especially in children. A systematic literature research (Medline, Pubmed) was performed to assess the risk associated with buprenorphine. The search, which was not limited to particular publication years, was performed with the key words buprenorphine AND toxicity (114 counts) AND children (4 counts) and buprenorphine AND mortality AND children (5 counts). In addition, the author obtained information from relevant websites (NIDA, SAMSHA) and pharmacovigilance data from the manufacturer of buprenorphine. Clinical and toxicological data suggest a low risk for fatal intoxications associated with bupreorphine in adults. Data from emergency units indicate a dramatic, 20-fold increase in buprenorphine exposure in children over the past decade, mostly in those under 6. The US ‘Researched Abuse, Diversion and Addiction-Related Surveillance’ (RADARS) system indicates a lower risk of severe opioid intoxications with buprenorphine than with other opioids, with no fatal outcomes recorded. Correspondingly, data from spontaneous reports to the surveillance programme of the manufacturer of buprenorphine (13,600 buprenorphine exposures, 4879 of these in children under six) show a serious medical outcome in 34% of children under the age of six but only one fatal outcome. Although exposure to buprenorphine and other opioids remains a significant concern in children, the drug seems rather to be safe with respect to severe outcomes, in particular death.

Introduction/Aims: ‘Hidden’ symptoms, or subtle cognitive deficits and long-term changes in mood, have been linked to the recreational use of 3, 4-methylenedioxymethamphetamine/MDMA, and are notionally present in non-heavy polydrug users. This study assessed the cognitive functioning and mood profiles of clinically diagnosed drug dependents who had never consumed MDMA, recreational drug users that had previously consumed MDMA, with both groups having not consumed illicit drugs for 6-months, and a control group with limited illicit drug use and no MDMA usage in their past. Methods: Cognitive functioning was assessed using the Cognitive Drug Research computerised cognitive assessment system and participants completed the Profile of Mood States and Beck Depression Inventory to assess their current mood and depression. Results: Participants in the clinically diagnosed drug dependent group scored significantly worse on the ‘Quality of Working Memory’ cognitive factor score than both the MDMA and control group (F (2, 33) = 5.75, p = 0.007). The control and clinical groups also differed on depression scores (U [16] = 13.00, p = 0.016) and Tension/Anxiety scores (U [16] = 16.00, p = 0.034), with the clinical group scoring significantly higher in both cases. The MDMA group did not differ from the control group on the measures of cognition or mood. Discussion/Conclusions: These results suggest that despite a 6-month prolonged abstinence the cognitive deficits ostensibly caused by ‘heavy’ usage or the dependence on or abuse of illicit drugs are not reversed by abstinence.

Tobacco dependence is the leading cause of preventable death and disability in the United States. While smoking prevalence among U.S. adults is 19.3%, the prevalence of smoking among methadone-maintained patients ranges between 73.5% and 94%. Most methadone-maintained smokers (76%-80%) desire to quit smoking; however only a minority of these smokers receive cessation treatment or referrals for smoking cessation intervention. Smoking cessation treatment in methadone-maintained patients has generally been successful in reducing the daily number of cigarettes smoked. Unfortunately, sustained cessation rates using nicotine replacement therapy and behavioral interventions have generally been low (0%-11%). Poor cessation outcomes may be partially explained by pharmacodynamic interactions between nicotine and methadone leading to increased reinforcement of smoking behavior. Further research is needed to improve smoking cessation rates in methadone-maintained patients.