Psilocybin as a treatment for addiction

“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”

“Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. to determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. the observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. the present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.”

“Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. in an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (cbt) for smoking cessation. twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. no significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. nine of 15 participants (60%) met criteria for ‘complete’ mystical experience. smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions. these results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.”

“Introduction: evidence based treatment for substance use disorders (sud) includes psychotherapy and pharmacotherapy. however, these are only partially effective. hallucinogens, such as psilocybin, may represent potential new treatment options for sud. this review provides a summary of (human) studies on the putative therapeutic effects of psilocybin, and discusses the receptor systems, brain regions and cognitive and emotional processes mediating psilocybin’s effects. psilocybin’s chemical structure is similar to that of serotonin. dysregulations in the serotonin system are associated with alterations in stress hormones, such as cortisol, and mood disorders. after psilocybin administration cortisol levels spike and activate the executive control network, with subsequent increased control over emotional processes, and relief of negative thinking and persistent negative emotions. preliminary data of ongoing alcohol and smoking addiction studies in humans shows promising effects of psilocybin administration on substance use. importantly, psilocybin has a low risk of toxicity and dependence and can be used safely under controlled clinical conditions.areas covered: this paper is a narrative review based on the search terms: psilocybin, substance use disorder, addiction, depression, serotonin. literature on potential efficacy and mechanisms of action of psilocybin in sud is discussed.expert commentary: recent positive findings with psilocybin need confirmation in well-designed placebo controlled randomized trials employing a large sample size.”

“Addictive disorders are very common and have devastating individual and social consequences. currently available treatment is moderately effective at best. after many years of neglect, there is renewed interest in potential clinical uses for classic hallucinogens in the treatment of addictions and other behavioral health conditions. in this paper we provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review other relevant research concerning hallucinogens, and suggest directions for future research. clinical trial data are very limited except for the use of lsd in the treatment of alcoholism, where a meta-analysis of controlled trials has demonstrated a consistent and clinically significant beneficial effect of high-dose lsd. recent pilot studies of psilocybin-assisted treatment of nicotine and alcohol dependence had strikingly positive outcomes, but controlled trials will be necessary to evaluate the efficacy of these treatments. although plausible biological mechanisms have been proposed, currently the strongest evidence is for the role of mystical or other meaningful experiences as mediators of therapeutic effects. classic hallucinogens have an excellent record of safety in the context of clinical research. given our limited understanding of the clinically relevant effects of classic hallucinogens, there is a wealth of opportunities for research that could contribute important new knowledge and potentially lead to valuable new treatments for addiction.”

“Scientific interest in serotonergic psychedelics (e.g., psilocybin and lsd; 5-ht2a receptor agonists) has dramatically increasedwithin the last decade. clinical studies administering psychedelicswith psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol.moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms,with potential advantages over existing antiinflammatory agents.wepropose that psychedelics exert therapeutic effects for psychiatric disorders by acutely destabilizing local brain network hubs and global network connectivity via amplification of neuronal avalanches, providing the occasion for brain network ‘resetting’ after the acute effects have resolved. antiinflammatory effectsmay hold promise for efficacy in treatment of inflammation-related nonpsy- chiatric as well as potentially for psychiatric disorders. serotonergic psychedelics operate through uniquemechanisms that showpromising effects for a variety of intractable, debilitating, and lethal disorders, and should be rigorously researched.”

“Recent research suggests that functional connectivity changes may be involved in the pathophy- siology of psychiatric disorders. hyperconnectivity in the default mode network has been asso- ciated with psychopathology, but psychedelic serotonin agonists like psilocybin may profoundly disrupt these dysfunctional neural network circuits and provide a novel treatment for psychiatric disorders. we have reviewed the current literature to investigate the efficacy and safety of psilocybin-assisted therapy for the treatment of psychiatric disorders. there were seven clinical trials that investigated psilocybin-assisted therapy as a treatment for psychiatric disorders related to anxiety, depression, and substance use. all trials demonstrated reductions in psychiatric rating scale scores or increased response and remission rates. there were large effect sizes related to improved depression and anxiety symptoms. psilocybin may also potentially reduce alcohol or tobacco use and increase abstinence rates in addiction, but the benefits of these two trials were less clear due to open-label study designs without statistical analysis. psilocybin-assisted therapy efficacy and safety appear promising, but more robust clinical trials will be required to support fda approval and identify the potential role in clinical psychiatry.”

“Psychedelic drugs have been used as treatments in indigenous cultures for thousands of years. yet, due to their legal status, there has been limited scientific research into the therapeutic potential of these compounds for psychiatric disorders. in the absence of other effective treatments however, researchers have begun again to systematically investigate such compounds and there is now evidence pointing to the use of psychedelic drugs in the treatment of addiction. in this review we focus on human evidence for the effectiveness of preparations used by indigenous cultures in the amazon (ayahausca) and africa (ibogaine) and worldwide (psilocybin), and more recently synthetised drugs such as the serotonergic hallucinogen lsd and the dissociative anaesthetic ketamine. potential mechanisms explored are anti-depressant effects, changes in neuroplasticity and existential psychological effects of these drugs.”

“Substances capable of changing the functions of the central nervous system are widely distributed in plant kingdom, and many of them were discovered by ancient food-gatherers at the dawn of humanity. in the old world only a few substances producing euphoria or altered states of consciousness and having habit-forming properties are still widely used. they are the products of poppy (opium, morphine), hemp (hashish, marijuana), and of fermentation of various organic materials alkohol. this list has recently been joined by the psilocybin-containing mushrooms. the addiction-forming compounds originated in the new world and widely spread are tobacco (nicotine) and cocaine. in the 19th and 20th, century the development of medicinal chemistry resulted in several synthetic compounds, originally proposed as therapeutics, such as barbiturates, benzodiazepines and amphetamines. due to legal problems, to avoid production of the substances already prohibited, many designer drugs were manufactured. in addition, several compounds were synthesized as recreational drugs. also some compounds that were not regarded as drugs, such as aromatic hydrocarbons and other cleansing agents, as well as steroids were found to have properties of dangerous, habit-forming agents. the attitude of society and the pattern of use of psychoactive substances have changed with time, particularly in the last decades. the active principles are now more addictive because of concentration, purification, chemical modifications and the way of ingestion, which now favors most rapid transport to the central nervous system. the substance abuse approaches the level of global epidemics, and the recent usage of drugs of addition is also reviewed.”

“Current treatments for addiction are frequently ineffective. hallucinogenic therapy has been indicated as helpful for a range of substance use disorders, yet this approach remains understudied and publicly unavailable. it is nonetheless a promising treatment, which has significant, long-term beneficial effects with single doses and a profile characterized by general safety, low toxicity, and non-addictiveness. however, pharmacological interventions, such as hallucinogens, should not be offered if the same effects (e.g. psychological insights/mystical experiences) and outcomes (e.g. decreased drug use) could be achieved absent pharmacological intervention. to date, there have been no clinical comparisons of drug-induced altered states with non-drug-induced states for addiction treatment. we propose and then outline a clinical trial to address this gap in knowledge. the proposed design would evaluate abstinence outcomes in a population of prescription opioid abusers after exposure to one of three conditions: a drug-induced altered state using psilocybin, a non-drug-induced altered state via hyperventilation (holotropic breathwork), and an active placebo with niacin. the outcomes of such a study would reveal important differences in therapeutic potential by discriminating hallucinogen-dependent effects from those psychological effects resulting from altered states.”

“After decades of sociopolitical obstacles, the field of psychiatry is experiencing a revived interest in the use of hallucinogenic agents to treat brain disorders. along with the use of ketamine for depression, recent pilot studies have highlighted the efficacy of classic serotonergic hallucinogens, such as lysergic acid diethylamide and psilocybin, in treating addiction, post-traumatic stress disorder, and anxiety. however, many basic pharmacological and toxicological questions remain unanswered with regard to these compounds. in this study, we discuss psychedelic medicine as well as the behavioral and toxicological effects of hallucinogenic drugs in zebrafish. we emphasize this aquatic organism as a model ideally suited to assess both the potential toxic and therapeutic effects of major known classes of hallucinogenic compounds. in addition, novel drugs with hallucinogenic properties can be efficiently screened using zebrafish models. well-designed preclinical studies utilizing zebrafish can contribute to the reemerging treatment paradigm of psychedelic medicine, leading to new avenues of clinical exploration for psychiatric disorders.”

“Numerous and diverse reports indicate the efficacy of shamanic plant adjuncts (e.g., iboga, ayahuasca, psilocybin) for the care and treatment of addiction, post-traumatic stress disorder, cancer, cluster headaches, and depression. this article reports on a first-person healing of lifelong asthma and atopic dermatitis in the shamanic context of the contemporary peruvian amazon and the sometimes digital ontology of online communities. the article suggests that emerging language, concepts, and data drawn from the sciences of plant signaling and behavior regarding ‘plant intelligence’ provide a useful heuristic framework for comprehending and actualizing the healing potentials of visionary plant ‘entheogens’ (wasson 1971) as represented both through firstperson experience and online reports. together with the paradigms and practices of plant signaling, biosemiotics provides a robust and coherent map for contextualizing the often reported experience of plant communication with ayahuasca and other entheogenic plants. the archetype of the ‘plant teachers’ (called doctores in the upper amazon) is explored as a means for organizing and interacting with this data within an epistemology of the “hallucination/ perception continuum (fischer 1975). ‘ecodelic’ is offered as a new linguistic interface alongside ‘entheogen’ (wasson 1971).”

“© 2016 elsevier inc.despite reports of apparent benefits, social and political pressure beginning in the late 1960s effectively banned scientific inquiry into psychedelic substances. covert examination of psychedelics persisted through the 1990s; the turn of the century and especially the past 10 years, however, has seen a resurgent interest in psychedelic substances (eg, lsd, ayahuasca, psilocybin). this chapter outlines relevant eeg and brain imaging studies evaluating the effects of psychedelics on the brain. this chapter also reviews evidence of the use of psychedelics as adjunct therapy for a number of psychiatric and addictive disorders. in particular, psychedelics appear to have efficacy in treating depression and alcohol-use disorders.”

“This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as lsd and psilocybin that exert their effects primarily through agonist activity at serotonin 2a (5ht2a) receptors. following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of lsd and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. a survey of possible mechanisms of clinically relevant effects is provided. the well-established safety of classic hallucinogens is reviewed. to provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of lsd treatment of alcoholism. in the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. the studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including phase 3, are now underway or being planned. although research has elucidated many of the acute neurobiological and psychological effects of classic hallucinogens on humans, animals, and in vitro systems, the mechanisms of clinically relevant persisting effects remain poorly understood.”

“Background: there is a long history of research interest in the therapeutic benefits of ‘psychedelic’ drugs including d-lysergic acid diethylamide (lsd), psilocybin (the active component in ’magic mushrooms’) and mdma (ecstasy). studies in psychiatry during the 1950s and 1960s reported benefits from their use in the treatment of a variety of disorders including schizophrenia, obsessive-compulsive disorder and alcoholism. however, inconsistent and adverse findings along with the widespread abuse of psychedelic drugs resulted in a ban on their use in clinical practice. renewed research interest emerged with the landmark johns hopkins study on psilocybin in 2008. further studies since then have examined the effectiveness of psilocybin in helping people to quit smoking and the effectiveness of psilocybin/lsd-assisted psychotherapy in the treatment of anxiety associated with end-stage cancer. the multidisciplinary association for psychedelic science (maps) has been a source of funding for international trials of psychedelic drugs, particularly trials that have focused on the use of mdma in war veterans suffering from treatment resistant post-traumatic stress disorder. objectives: to increase awareness of the therapeutic use of psychedelic drugs and to encourage further research within australia. methods: a review of the current literature on psychedelic drug research. findings: there is a growing body of evidence showing that psychedelic drugs can make a major contribution to effective treatment in psychiatry. conclusions: many arguments against the use of psychedelic drugs are moral rather than medical. further research and investigation is needed to lift the taboo on these drugs and reveal their potential benefits.”

“Background:recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015.aims:the aims of this study were as follows: (1) to identify perceived mechanisms of change leading to smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process.methods:participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. semi-structured interviews were conducted with 12 of the 15 participants. data were analysed using thematic analysis.results:participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. participants emphasised that …”

“Background: clinical research on classic hallucinogens in treatment of addiction was halted abruptly in the early 1970s, and is only now resuming. the purpose of this presentation is to 1) review past clinical trials of classic hallucinogens for addiction 2) discuss possible mechanisms of action, and 3) present design and preliminary results of two ongoing pilot studies of psilocybin in the treatment of nicotine and alcohol dependence. methods: a review was conducted of published controlled trials of classic hallucinogens for treatment of addictions. in addition, a broader literature review aimed to identify possible psychological and biological mechanisms of action. current open-label trials are investigating effects of psilocybin on nicotine dependence and alcohol dependence. the johns hopkins smoking cessation study includes 3 psilocybin sessions at 4-week intervals in doses of 20- 30 mg/70 kg, combined with cognitive behavioral smoking cessation treatment. the unm alcohol dependence study includes 2 psilocybin sessions one month apart, at doses of 0.3-0.4 mg/kg, combined with motivational enhancement therapy. results: numerous studies in the 1960s and early 1970s investigated the use of lsd in the treatment of alcoholism. a recent meta-analysis of 6 randomized controlled trials of lsd administered in a single high dose for treatment of alcoholism (total n=536) demonstrated that the overall effect size of lsd treatment was substantial and highly consistent across studies, with an odds ratio for post-treatment improvement of 1.96 (95% ci 1.36-2.84). trials investigating other classic hallucinogens and other addictions had methodological problems that limit confidence in their findings. the psychedelic model hypothesized that an overwhelming nullpeak-psychedelicnull or mystical experience could bring about lasting change in personality and addictive behavior. although this mechanism has not been demonstrated directly in addiction trials, the hypothesis is consistent with data including 1) effects of psilocybin in normal participants; 2) qualitative and quantitative research on transformative/mystical experiences leading to abstinence in addicts; and 3) decreases in substance use among members of religions that use classic hallucinogens sacramentally. although basic research on anti-addictive effects of classic hallucinogens is lacking, 5ht2a receptor-mediated increases in expression of bdnf and gdnf are potentially relevant to changes in substance use …”

“Background: evidence suggests that classic hallucinogens have clinically relevant effects in alcohol and drug addiction. it is hypothesized that acute pharmacological and psychological effects trigger longer-term changes in psychological variables such as mood, craving, and selfefficacy, and that these changes in turn lead to persisting improvement in substance use behavior. this report explores the effects of psilocybin administration on changes in mood, alcohol craving, and self-efficacy, and the relationship of these changes to short-term drinking outcomes that were previously reported. methods: ten patients with dsm-iv alcohol dependence received psilocybin 0.3 mg/kg po in a supervised 8-hour session after 4 weeks of outpatient psychotherapy. nine of these participants remained in the study for at least 4 additional weeks, during which no psilocybin was administered. measures of acute medication effects included the total score from the mystical experience scale, the general scale from the altered states of consciousness scale (5d-asc), and the intensity subscale of the hallucinogen rating scale. measures of mood (the profile of mood states), self-efficacy (the alcohol abstinence self-efficacy scale, confidence subscale), craving (the penn. alcohol craving scale), and drinking were obtained at baseline and at intervals during and following treatment. drinking outcomes were percent drinking days and percent heavy drinking days. results: mean profile of mood states subscale scores did not change significantly in the week following psilocybin administration (week 5) relative to the week before (week 4). however, individual changes in tension, depression, vigor, and confusion were significantly (p <.05) correlated with one or more of the three measures of the subjective experience during the first psilocybin session (r =.680 t<920). in all cases, more favorable mood outcomes were observed in participants who had stronger subjective experiences. changes in mood symptoms at week 5 were significantly correlated with changes in drinking during the month following the first psilocybin session (weeks 5-8) relative to the month before (weeks 1-4). similarly, craving was not significantly decreased at week 5, but change in craving was strongly correlated (r4.8, p<.01) with two of three measures of subjective experience intensity, and this change in craving was correlated with subsequent changes drinking outcomes in weeks 5-8 (r 4.7, p <.05). significant correla…”

“Aims: to examine instances in which psychedelic use may have led to reduced drug use. methods: an anonymous online survey assessed demographics, drug use history, addiction/withdrawal severity, and data on participants’ psychedelic-occasioned experience and perceived effects on substance use. results: participants (n= 301) were predominantly white (87%), males (67%), in the us (60%), mean age 32 yrs. participants reported reductions in alcohol (53% of participants), cannabis (19%), opioid (17%), and stimulant (11%) use after taking a psychedelic. 61% reported continuous substance use reduction lasting >=1 yr. since their reference psychedelic experience. psilocybin (37%) and lsd (34%) were most commonly associated with reduced substance use. 90% of participants met dsm 5 criteria for a substance use disorder (sud) before their reference psychedelic experience, with 64% having a severe sud. afterward, 19% met criteria for a sud, with 4% meeting severe sud criteria. 159 reported reduced alcohol use from a mode of 5-6 drinks on >=4 days/week to a mode of 1-2 drinks/month, with 21% (n = 34) reporting total alcohol abstinence since their psychedelic use. 57 reported reduced cannabis use from a mode of 1-2 uses on >=4 days/week to a mode of 1-2 uses/month, with 21% (n = 12) reporting total cannabis abstinence since their psychedelic use. 51 reported opioid reduction from a mode of 1-2 uses on >=4 days/week to a mode of total opioid abstinence (n = 33; 65%) since their psychedelic use. 34 reported stimulant reduction from a mode of 1-4 uses on >=4 days/week to a mode of total stimulant abstinence (n = 20; 59%) since their psychedelic use. conclusions: psychedelic use may sometimes lead to persisting reductions in alcohol and drug use, consistent with prior research suggesting efficacy of psychedelic-facilitated addiction treatment. further controlled research in this area is indicated.”

“© 2018 informa uk limited, trading as taylor & francis group background: the ceremonial use of psychoactive/hallucinogenic plant based drugs, such as ayahuasca, psilocybin and others, is a growing trend in the united states (us) and globally. to date, there has been little research documenting how many people are using psychoactive substances in this context, who the users are, what benefits/risks exist in the use of these drugs and the relationship between ceremonial drug use and recreational drug use. in this paper we describe a cohort of plant medicine facilitators in the us and explore how they differentiate plant medicine use from recreational drug use. methods: using modified ethnography, individual interviews were conducted in 2016 with 15 participants who are currently facilitating plant medicine ceremonies in the us. descriptive content analysis was performed to discover themes and to inform a larger mixed-method study. results: ceremonial drug use was seen by participants as a natural healing and treatment modality used in the context of community and ritual. three main themes were identified relating to participants’ differentiation between ceremonial plant medicine use and recreational drug use: (1) participants see a clear delineation between plant medicine use and recreational drug use; (2) plant medicine is seen as a potential treatment for addiction, but concerns exist regarding potential interference with recovery; and (3) plant medicine use may influence recreational use. conclusions: more research is needed on who is using plant medicine, motivators for use, perceived and real risks and benefits of plant medicine use and harm reduction techniques regarding safe ingestion.”

“The main scope of this review is to expose the main advances regarding recent research of psychedelic substances in the neurociences and their potential psychotherapeutic applications. psilocybin, a 5-ht2a receptor agonist has been associated with reduced activity in the default- mode network (commonly activated during introspection and self-reflection), enhanced access to biographical memories, positive emotional attentional bias and a reduction on anxiety and mood symptoms. the administration of 3,4-methylenedioxy-n- methylamphetamine (mdma) could significantly aid the psychotherapeutic process in patients with post-traumatic stress disorder by strengthening the therapeutic alliance through the release of oxytocin, as well as facilitating emotional regulation from frontal areas to the amygdala during the recollection of traumatic memories. furthermore, the administration of ayahuasca (an amazonic beverage containing dimethyltryptamine, which binds with the 5-ht2a receptor) and ketamine (a nmda receptor agonist) in pilot studies has resulted in reduced problematic use of cocaine, heroine, alcohol and tobacco, as well as reported reduction in craving in addiction. while modern research with substances containing psychedelic properties is still young, initial findings suggest the need of expanding the number of studies in order to further clarify their potential risks, benefits and action mechanisms associated to their administration.”

“We at the heffter research institute appreciate dr. dakwar’s overview of the history and present environment of hallucinogen research. (cpdd news and views, this volume). with the notable exceptions we address below, he gives a balanced assessment of the potential risks and benefits of hallucinogen research, and we generally agree with his perspective, including the need for government research funds. we are writing to answer some concerns that dr. dakwar raises. his opinion article states that heffter has ‘a clear agenda: to see hallucinogens reinstated as viable treatment modalities.’ it is true that heffter-supported scientists are deeply curious about their chosen fields and they conduct research they hope will prove truly helpful. we would hope that this applies to scientists everywhere. to assure quality and integrity in the presence of possible investigator bias, the scientific method, as it is pursued today, includes numerous checks and balances. to name some of them: mentors and peers assist researchers in developing hypotheses and methods. the fda and dea review protocols as required. irbs review protocols, often with greater scrutiny for hallucinogen research. finally, quality journals implement rigorous outside review processes prior to accepting papers for publication. dr. dakwar notes correctly that heffter is shepherding private funding and coordinating research with hallucinogens. any concern that raises is not unique to heffter. the scientific process includes checks and balances deemed sufficient to manage potential conflicts of interest, including the exclusion of board members from deliberations on funding their research. what is more, in addition to the safeguards listed above, heffter’s involvement provides another assurance of quality science, as heffter sends all grant proposals out for external anonymous peer review and rigorously reviews each proposed study prior to funding. these reviewers are among the most experienced experts with respect to each specific research topic at hand. altogether, we stand by each of the more than 80 peer-reviewed publications that heffter funding has supported to date. we would like to take this opportunity to mention just a few of these contributions to basic clinical science and, we hope, eventually to novel therapies that can provide relief in cases where today’s conventional treatments fall short. from our supported laboratory at the university of z�rich, detailed elucidations of the effect of…”