Psychedelic Science, Contemplative Practices, and Indigenous and Other Traditional Knowledge Systems: Towards Integrative Community-Based Approaches in Global Health.

As individuals and communities around the world confront mounting physical, psychological, and social threats, three complimentary mind-body-spirit pathways toward health, wellbeing, and human flourishing remain underappreciated within conventional practice among the biomedical, public health, and policy communities. This paper reviews literature on psychedelic science, contemplative practices, and Indigenous and other traditional knowledge systems to make the case that combining them in integrative models of care delivered through community-based approaches backed by strong and accountable health systems could prove transformative for global health. Both contemplative practices and certain psychedelic substances reliably induce self-transcendent experiences that can generate positive effects on health, well-being, and prosocial behavior, and combining them appears to have synergistic effects. Traditional knowledge systems can be rich sources of ethnobotanical expertise and repertoires of time-tested practices. A decolonized agenda for psychedelic research and practice involves engaging with the stewards of such traditional knowledges in collaborative ways to codevelop evidence-based models of integrative care accessible to the members of these very same communities. Going forward, health systems could consider Indigenous and other traditional healers or spiritual guides as stakeholders in the design, implementation, and evaluation of community-based approaches for safely scaling up access to effective psychedelic treatments.

Policy considerations that support equitable access to responsible, accountable, safe, and ethical uses of psychedelic medicines.

There is mounting evidence suggesting psychedelic and entactogen medicines (namely psilocybin and 3,4-methylenedioxymethamphetamine [MDMA]), in conjunction with proper psychosocial support, hold the potential to provide safe, rapid acting, and robust clinical improvements with durable effects. In the US, both psilocybin and MDMA have been granted Breakthrough Therapy designations by the US Food and Drug Administration and may potentially receive full FDA approval with similar regulatory considerations occurring in multiple countries. At the same time, regulatory changes are poised to increase access to legal or decriminalized psychedelic use in various non-medical settings. This review provides a brief discussion on the historical use of psychedelic medicines, the status of the empirical evidence, and numerous significant policy considerations that must be thoughtfully addressed regarding standards-of-practice, consumer protection, engagement of communities, safeguarding access for all, and developing data standards, which supports the responsible, accountable, safe, and ethical uses of these medicines in clinical, faith-based, and other contexts. We provide suggestions for how public health and harm reduction can be supported through a public-private partnership that engages a community of stakeholders from various disciplines in the co-creation and dissemination of best practices and public policies.

If the Doors of Perception Were Cleansed, Would Chronic Pain be Relieved? Evaluating the Benefits and Risks of Psychedelics.

Psychedelic substances have played important roles in diverse cultures, and ingesting various plant preparations to evoke altered states of consciousness has been described throughout recorded history. Accounts of the subjective effects of psychedelics typically focus on spiritual and mystical-type experiences, including feelings of unity, sacredness, and transcendence. Over the past 2 decades, there has been increasing interest in psychedelics as treatments for various medical disorders, including chronic pain. Although concerns about adverse medical and psychological effects contributed to their controlled status, contemporary knowledge of psychedelics suggests that risks are relatively rare when patients are carefully screened, prepared, and supervised. Clinical trial results have provided support for the effectiveness of psychedelics in different psychiatric conditions. However, there are only a small number of generally uncontrolled studies of psychedelics in patients with chronic pain (eg, cancer pain, phantom limb pain, migraine, and cluster headache). Challenges in evaluating psychedelics as treatments for chronic pain include identifying neurobiologic and psychosocial mechanisms of action and determining which pain conditions to investigate. Truly informative proof-of-concept and confirmatory randomized clinical trials will require careful selection of control groups, efforts to minimize bias from unblinding, and attention to the roles of patient mental set and treatment setting. PERSPECTIVE: There is considerable promise for the use of psychedelic therapy for pain, but evidence-based recommendations for the design of future studies are needed to ensure that the results of this research are truly informative.

Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study.

RATIONALE: Standard therapeutic approaches to reduce social anxiety in autistic adults have limited effectiveness. Since 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy shows promise as a treatment for other anxiety disorders, a blinded, placebo-controlled pilot study was conducted. OBJECTIVES: To explore feasibility and safety of MDMA-assisted psychotherapy for reduction of social fear and avoidance that are common in the autistic population. METHODS: Autistic adults with marked to very severe social anxiety were randomized to receive MDMA (75 to 125 mg, n = 8) or inactive placebo (0 mg, n = 4) during two 8-h psychotherapy sessions (experimental sessions) in a controlled clinical setting. Double-blinded experimental sessions were spaced approximately 1 month apart with 3 non-drug psychotherapy sessions following each. The primary outcome was change in Leibowitz Social Anxiety Scale (LSAS) Total scores from Baseline to one month after the second experimental session. Outcomes were measured again six months after the last experimental session. RESULTS: Improvement in LSAS scores from baseline to the primary endpoint was significantly greater for MDMA group compared to the placebo group (P = 0.037), and placebo-subtracted Cohen's d effect size was very large (d = 1.4, CI - 0.074, 2.874). Change in LSAS scores from baseline to 6-month follow-up showed similar positive results (P = 0.036), with a Cohen's d effect size of 1.1 (CI - 0.307, 2.527). Social anxiety remained the same or continued to improve slightly for most participants in the MDMA group after completing the active treatment phase. CONCLUSIONS: This pilot trial demonstrated rapid and durable improvement in social anxiety symptoms in autistic adults following MDMA-assisted psychotherapy. Initial safety and efficacy outcomes support expansion of research into larger samples to further investigate this novel treatment for social anxiety. TRIAL REGISTRATION: clinicaltrials.gov identifier, NCT02008396.

Is LSD toxic?

LSD (lysergic acid diethylamide) was discovered almost 75 years ago, and has been the object of episodic controversy since then. While initially explored as an adjunctive psychiatric treatment, its recreational use by the general public has persisted and on occasion has been associated with adverse outcomes, particularly when the drug is taken under suboptimal conditions. LSD's potential to cause psychological disturbance (bad trips) has been long understood, and has rarely been associated with accidental deaths and suicide. From a physiological perspective, however, LSD is known to be non-toxic and medically safe when taken at standard dosages (50-200µg). The scientific literature, along with recent media reports, have unfortunately implicated "LSD toxicity" in five cases of sudden death. On close examination, however, two of these fatalities were associated with ingestion of massive overdoses, two were evidently in individuals with psychological agitation after taking standard doses of LSD who were then placed in maximal physical restraint positions (hogtied) by police, following which they suffered fatal cardiovascular collapse, and one case of extreme hyperthermia leading to death that was likely caused by a drug substituted for LSD with strong effects on central nervous system temperature regulation (e.g. 25i-NBOMe). Given the renewed interest in the therapeutic potential of LSD and other psychedelic drugs, it is important that an accurate understanding be established of the true causes of such fatalities that had been erroneously attributed to LSD toxicity, including massive overdoses, excessive physical restraints, and psychoactive drugs other than LSD.

Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA.

4-phosphorloxy-N,N-dimethyltryptamine (psilocybin) and methylenedioxymethamfetamine (MDMA), best known for their illegal use as psychedelic drugs, are showing promise as therapeutics in a resurgence of clinical research during the past 10 years. Psilocybin is being tested for alcoholism, smoking cessation, and in patients with advanced cancer with anxiety. MDMA is showing encouraging results as a treatment for refractory post-traumatic stress disorder, social anxiety in autistic adults, and anxiety associated with a life-threatening illness. Both drugs are studied as adjuncts or catalysts to psychotherapy, rather than as stand-alone drug treatments. This model of drug-assisted psychotherapy is a possible alternative to existing pharmacological and psychological treatments in psychiatry. Further research is needed to fully assess the potential of these compounds in the management of these common disorders that are difficult to treat with existing methods.

MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults.

The first study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of social anxiety in autistic adults commenced in the spring of 2014. The search for psychotherapeutic options for autistic individuals is imperative considering the lack of effective conventional treatments for mental health diagnoses that are common in this population. Serious Adverse Events (SAEs) involving the administration of MDMA in clinical trials have been rare and non-life threatening. To date, MDMA has been administered to over 1133 individuals for research purposes without the occurrence of unexpected drug-related SAEs that require expedited reporting per FDA regulations. Now that safety parameters for limited use of MDMA in clinical settings have been established, a case can be made to further develop MDMA-assisted therapeutic interventions that could support autistic adults in increasing social adaptability among the typically developing population. As in the case with classic hallucinogens and other psychedelic drugs, MDMA catalyzes shifts toward openness and introspection that do not require ongoing administration to achieve lasting benefits. This infrequent dosing mitigates adverse event frequency and improves the risk/benefit ratio of MDMA, which may provide a significant advantage over medications that require daily dosing. Consequently, clinicians could employ new treatment models for social anxiety or similar types of distress administering MDMA on one to several occasions within the context of a supportive and integrative psychotherapy protocol.

PTSD symptom reports of patients evaluated for the New Mexico Medical Cannabis Program.

BACKGROUND: New Mexico was the first state to list post-traumatic stress disorder (PTSD) as a condition for the use of medical cannabis. There are no published studies, other than case reports, of the effects of cannabis on PTSD symptoms. The purpose of the study was to report and statistically analyze psychometric data on PTSD symptoms collected during 80 psychiatric evaluations of patients applying to the New Mexico Medical Cannabis Program from 2009 to 2011. METHODS: The Clinician Administered Posttraumatic Scale for DSM-IV (CAPS) was administered retrospectively and symptom scores were then collected and compared in a retrospective chart review of the first 80 patients evaluated. RESULTS: Greater than 75% reduction in CAPS symptom scores were reported when patients were using cannabis compared to when they were not. CONCLUSIONS: Cannabis is associated with reductions in PTSD symptoms in some patients, and prospective, placebo-controlled study is needed to determine efficacy of cannabis and its constituents in treating PTSD.

Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer.

CONTEXT: Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer. OBJECTIVE: To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety. DESIGN: A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin. SETTING: A clinical research unit within a large public sector academic medical center. PARTICIPANTS: Twelve adults with advanced-stage cancer and anxiety. MAIN OUTCOME MEASURES: In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment. RESULTS: Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance. CONCLUSIONS: This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00302744.

An emergency department intervention for linking pediatric suicidal patients to follow-up mental health treatment.

OBJECTIVE: Suicide is the third leading cause of death among adolescents. Many suicidal youths treated in emergency departments do not receive follow-up treatment as advocated by the National Strategy for Suicide Prevention. Two strategies for improving rates of follow-up treatment were compared. METHODS: In a randomized controlled trial, suicidal youths at two emergency departments (N=181; ages ten to 18) were individually assigned between April 2003 and August 2005 to one of two conditions: an enhanced mental health intervention involving a family-based cognitive-behavioral therapy session designed to increase motivation for follow-up treatment and safety, supplemented by care linkage telephone contacts after emergency department discharge, or usual emergency department care enhanced by provider education. Assessments were conducted at baseline and approximately two months after discharge from the emergency department or hospital. The primary outcome measure was rates of outpatient mental health treatment after discharge. RESULTS: Intervention patients were significantly more likely than usual care patients to attend outpatient treatment (92% versus 76%; p=.004). The intervention group also had significantly higher rates of psychotherapy (76% versus 49%; p=.001), combined psychotherapy and medication (58% versus 37%; p=.003), and psychotherapy visits (mean 5.3 versus 3.1; p=.003). Neither the emergency department intervention nor community outpatient treatment (in exploratory analyses) was significantly associated with improved clinical or functioning outcomes. CONCLUSIONS: Results support efficacy of the enhanced emergency department intervention for improving linkage to outpatient mental health treatment but underscore the need for improved community outpatient treatment to prevent suicide, suicide attempts, and poor clinical and functioning outcomes for suicidal youths treated in emergency departments.

Ayahuasca in adolescence: a neuropsychological assessment.

The purpose of the study was to evaluate neuropsychologically adolescents who use ayahuasca in a religious context. A battery of neuropsychological tests was administered to adolescents who use ayahuasca. These subjects were compared to a matched control group of adolescents who did not use ayahuasca. The controls were matched with regards to sex, age, and education. The neuropsychological battery included tests of speeded attention, visual search, sequencing, psychomotor speed, verbal and visual abilities, memory, and mental flexibility. The statistical results for subjects from matched controls on neuropsychological measures were computed using independent t-tests. Overall, statistical findings suggested that there was no significant difference between the two groups on neuropsychological measures. Even though, the data overall supports that there was not a difference between ayahuasca users and matched controls on neuropsychological measures, further studies are necessary to support these findings.

Ayahuasca in adolescence: a preliminary psychiatric assessment.

Ayahuasca is believed to be harmless for those (including adolescents) drinking it within a religious setting. Nevertheless controlled studies on the mental/ psychiatric status of ritual hallucinogenic ayahuasca concoction consumers are still lacking. In this study, 40 adolescents from a Brazilian ayahuasca sect were compared with 40 controls matched on sex, age, and educational background for psychiatric symptomatology. Screening scales for depression, anxiety, alcohol consumption patterns (abuse), attentional problems, and body dysmorphic disorders were used. It was found that, compared to controls, considerable lower frequencies of positive scoring for anxiety, body dismorphism, and attentional problems were detected among ayahuasca-using adolescents despite overall similar psychopathological profiles displayed by both study groups. Low frequencies of psychiatric symptoms detected among adolescents consuming ayahuasca within a religious context may reflect a protective effect due to their religious affiliation. However further studies on the possible interference of other variables in the outcome are necessary.