million people affected worldwide
Current Treatments
Psychedelic research currently is in Not Applicable
Safety is of the utmost importance when discussing any sort of drug. Not only do scientists have to prove drugs are therapeutically effective, but they must also ensure drugs are safe for human consumption. Various procedures are in place in order to determine the safety and efficacy of drugs. Regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are tasked with ensuring these procedures are strictly adhered to during the drug development process. The development process generally begins with the submission of an Investigational New Drug (IND) application which contains the results of preclinical tests of the drug in animal models. The IND is then reviewed by the FDA or EMA and an independent panel consisting of both scientists and non-scientists. Clinical trials involving humans can only begin if the review finds that the proposed clinical trial protocols are satisfactory. Researchers must explicitly state the drug under investigation, what dose it will be administered in and the type of people it will be administered to, amongst other things. Once approved for testing, clinical trials can begin. In Phase-I of the clinical trial process, healthy volunteers are given the drug in order to determine levels of toxicity, how the drug is metabolized and if there are any side effects. Phase-II is more focused on the effectiveness of the drug although safety is continually evaluated. Phase-III studies then begin which further assess safety and effectiveness in a much larger and more diverse sample. Upon completion of Phase-III, those sponsoring the trials must submit a New Drug Application (NDA) to the regulatory authorities before bringing the drug to market. The NDA contains all the data for both animal and human studies to further assess safety and effectiveness (FDA, 2017). The entire process of drug development is a lengthy and expensive process, with many drug candidates failing at some stage of the process. At present, a whole range of psychedelics drugs are at various stages of the clinical trial process, proving that these drugs are both safe and effective.
Psychedelics have a relationship with society like no other pharmacological agent. Research into this class of psychoactive drugs in the middle of the 20th century is notoriously marred with methodological flaws and practices which are considered unsafe by today’s standards. For years the media have largely portrayed psychedelics as extremely dangerous drugs (Nichols, 2016). Today, researchers must contend with the fallout from this era of research in order to prove that these drugs are both effective and safe. To do so, psychedelics are being put through the gold-standard testing procedures of drug development, randomized-controlled trials (RCTs). In RCTs, the study population is carefully selected and then randomly assigned to either a treatment group or a control group. The treatment group receives the drug being studied and the control group receives a placebo, all while randomization reduces the likelihood of biased results (Hariton & Locascio, 2018). However, treatment models using psychedelics do not fully align with this gold-standard and problems do exist. Firstly, RCTs do not account for how extra pharmacological variables influence the drug experience yet these extra pharmacological variables have been deemed essential to facilitating the psychedelic experience (Carhart-Harris et al., 2018). Furthermore, the effects of psychedelics are potent which makes blinding in these trials difficult (Muthukumaraswamy et al., 2021). Regulatory bodies also tend to require large sample sizes to prove a drug’s efficacy and safety but at present, sample sizes in trials using psychedelics tend to be quite low. Reasons for this could relate to psychedelics being expensive and difficult to procure, as well as psychedelic-assisted psychotherapy being a labour-intensive process given the time required for preparation, integration and the experience itself. Nevertheless, researchers are working within the regulatory requirements with great success.
On the basis of a wide range of research, psychedelics are considered physiologically safe and do not lead to dependence or addiction (Nichols, 2016). This evidence stands in contrast with psychedelics current position as Schedule I substances, which have no accepted medical value and also possess high abuse potential. Interestingly, Matthew Johnson and his colleagues at Johns Hopkins used the very same factors of the Control Substance Act which classify psychedelics as Schedule I substances to assess the abuse potential of psilocybin. Johnson and his colleagues found that although potential harms exist for unprepared, unsupervised users, and in those with or predisposed to psychotic disorders, modern research addresses these concerns with dose control, patient screening, preparation and follow-up, and session supervision in a medical facility (Johnson et al., 2018). Moreover, these researches suggest that psilocybin would be more appropriately classed as Schedule IV substances given its therapeutic potential and safety.
What makes psychedelics all the more interesting is the ability of extra pharmacological factors to influence the experience, be it positively or negatively. As a result, therapy rooms in which psychedelics are administered are manipulated to ensure patients have a safe and positive experience. Again, Johnson and his colleagues at John Hopkins are accredited with writing the go-to guidelines for conducting psychedelic research in humans (Johnson et al., 2008). In their seminal paper, Johnson and his team emphasize that the physical environment be free of extraneous medical or research equipment, in combination with careful volunteer screening, volunteer preparation and interpersonal support from two or more trained monitors, may help to minimize the probability of acute psychological distress during psychedelic studies and ensure the safety of patients (Johnson et al., 2008).
Overall, adverse physiological reactions to classic psychedelics are rare (Nichols, 2016). Nonetheless, psychedelics can create severe psychological distress and should be approached with caution. As psychedelic research is progressing, researchers and regulators are working together to realize the potential of psychedelic drugs in a manner that is safe for all those involved.
References
- FDA. (2017). The FDA’s Drug Review Process: Ensuring Drugs Are Safe and Effective. Food and Drug Administration. Retrieved from https://www.fda.gov/drugs/information-consumers-and-patients-drugs/fdas-drug-review-process-ensuring-drugs-are-safe-and-effective
- Hariton, E., & Locascio, J. (2018). Randomised controlled trials—the gold standard for effectiveness research. BJOG. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235704/#
- Johnson, M., Griffiths, R., Hendricks, P., & Henningfield, J. (2018). The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology, 143-166. Retrieved from https://blossomanalysis.com/papers/the-abuse-potential-of-medical-psilocybin-according-to-the-8-factors-of-the-controlled-substances-act/
- Johnson, M., Richards, W., & Griffiths, R. (2008). Human Hallucinogen Research: Guidelines for Safety. Journal of Psychopharmacology, 603-620. Retrieved from https://blossomanalysis.com/papers/human-hallucinogen-research-guidelines-for-safety/
- Muthukumaraswamy, S., Forsyth, A., & Lumley. (2021). Blinding and expectancy confounds in psychedelic randomized controlled trials. Expert Review of Clinical Pharmacology, 1133-1152. Retrieved from https://blossomanalysis.com/papers/blinding-and-expectancy-confounds-in-psychedelic-randomised-controlled-trials/
- Nichols, D. (2016). Psychedelics. Pharmacological Reviews, 264-355. Retrieved from https://blossomanalysis.com/papers/psychedelics/
Highlighted Institutes
These are the institutes, from companies to universities, who are working on Safety.
Highlighted People
These are some of the best-known people, from researchers to entrepreneurs, working on Safety.
Linked Research Papers about Safety
Reactivations after 5-methoxy-N,N-dimethyltryptamine use in naturalistic settings: An initial exploratory analysis of the phenomenon’s predictors and its emotional valence
Ascending-dose study of noribogaine in healthy volunteers: Pharmacokinetics, pharmacodynamics, safety, and tolerability
Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions
Experienced drug users assess the relative harms and benefits of drugs: a web-based survey
Making a medicine out of MDMA
Attitudes and Beliefs about the Therapeutic Use of Psychedelic Drugs among Psychologists in the United States
Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings – Evaluating the Kosmicare Project at Boom Festival
Lysergic acid diethylamide: side effects and complications
Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant
The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation
Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action
Psilocybin Newspaper Coverage – Sentiment and Frequency (1989-2020)
Neurotoxicity and LSD treatment: a follow-up study of 151 patients in Denmark
Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers
Psychological and cardiovascular effects and short-term sequelae of MDMA (“ecstasy”) in MDMA-naıve healthy volunteers
A Survey of American Psychiatrists’ Attitudes Toward Classic Hallucinogens
Psychedelic use and intimate partner violence
Discriminative Stimulus Effects of Substituted Tryptamines in Rats
Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function
Are Ecstasy Induced Serotonergic Alterations Overestimated For The Majority Of Users?
A rapid scoping review of harm reduction strategies for ecstasy (MDMA) users in recreational settings
Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study
Therapeutic (Sub)stance: Current practice and therapeutic conduct in preparatory sessions in substance-assisted psychotherapy—A systematized review
Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects
Research abuses against people of colour and other vulnerable groups in early psychedelic research
The epidemiology of mescaline use: Pattern of use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects
Hallucinogenic Persisting Perception Disorder: A Case Series and Review of the Literature
“Meeting the Medicine Halfway”: Ayahuasca Ceremony Leaders’ Perspectives on Preparation and Integration Practices for Participants
Mescaline: The forgotten psychedelic
The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act
Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects
On Perception and Consciousness in HPPD: A Systematic Review
Adverse Reactions to Psychedelic Drugs - A Review of the Literature
Acute effects of 3, 4-methylenedioxymethamphetamine (MDMA) on behavioral measures of impulsivity: alone and in combination with alcohol
Effects of a β-blocker on the cardiovascular response to MDMA (Ecstasy)
A Nationwide Study Comparing Mental Health Professionals' Willingness to Try Hallucinogenic Drugs in Basic Research or Clinical Practice
Safer Tripping: Serotonergic Psychedelics and Drug Checking. Submission and Detection Rates, Potential Harms, and Challenges for Drug Analysis
The influence of ceremonial settings on mystical and challenging experiences occasioned by ayahuasca: A survey among ritualistic and religious ayahuasca users
Human hallucinogen research: guidelines for safety
Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives
Epidemiology of hospitalizations with hallucinogen use disorder: a 17-year U.S. National study
New insights into the clinical and nonclinical effects of psychedelic substances: An integrative review.
Hallucinogen persisting perceptual disorder: a scoping review covering frequency, risk factors, prevention and treatment
Prospective association of psychological pain and hopelessness with suicidal thoughts
Pharmacokinetics and concentration-effect relationship of oral LSD in humans
Sex differences in sub-anesthetic ketamine’s antidepressant effects and abuse liability
Why was early therapeutic research on psychedelic drugs abandoned?
Effects of the psychedelic amphetamine MDA (3, 4-methylenedioxyamphetamine) in healthy volunteers
Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults
Magic Mushroom Use: A Qualitative Interview Study of Post-Trip Impacts and Strategies for Optimizing Experiences
Ketanserin reverses the acute response to LSD in a randomized, double-blind, placebo-controlled, crossover study in healthy subjects
Developmental outcomes of 3,4-methylenedioxymethamphetamine (ecstasy)-exposed infants in the UK
Pyretogenic effect of lysergic acid diethylamide
LSD-associated “Alice in Wonderland Syndrome”(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report
Recreation and Realization: Reported Motivations of Use Among Persons Who Consume Psychedelics in Non-Clinical Settings
Pharmacological effects of methylone and MDMA in humans
Serotonin toxicity of serotonergic psychedelics
Ayahuasca and Public Health: Health Status, Psychosocial Well-Being, Lifestyle, and Coping Strategies in a Large Sample of Ritual Ayahuasca Users
Psychedelic perceptions: mental health service user attitudes to psilocybin therapy
Key interindividual determinants in MDMA pharmacodynamics
The readiness of psychiatrists to implement psychedelic-assisted psychotherapy
Do hallucinogens cause residual neuropsychological toxicity?
Ayahuasca and Public Health II: Health Status in a Large Sample of Ayahuasca-Ceremony Participants in the Netherlands
Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans
Day trip to hell: A mixed methods study of challenging psychedelic experiences
Family of Structurally Related Bioconjugates Yields Antibodies with Differential Selectivity against Ketamine and 6-Hydroxynorketamine
Long-term effects of psychedelic drugs: A systematic review
Dose-response study of N,N-dimethyltryptamine in humans: subjective effects and preliminary results of a new rating scale
Effects of Setting on Psychedelic Experiences, Therapies, and Outcomes: A Rapid Scoping Review of the Literature
Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers
Contextual Parameters Associated with Positive and Negative Mental Health in Recreational Psychedelic Users
Great Expectations: Recommendations for improving the methodological rigor of psychedelic clinical trials
Kratom Abuse Potential 2021: An Updated Eight Factor Analysis
Adverse experiences resulting in emergency medical treatment seeking following the use of magic mushrooms
Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database
The adverse events of ibogaine in humans: an updated systematic review of the literature (2015-2020)
Effect of Ritualistic Consumption of Ayahuasca on Hepatic Function in Chronic Users
Safety pharmacology of acute LSD administration in healthy subjects
Administration of N,N-dimethyltryptamine (DMT) in psychedelic therapeutics and research and the study of endogenous DMT
Psilocybin therapy of psychiatric disorders is not hampered by hERG potassium channel-mediated cardiotoxicity
Self-Experiments with Psychoactive Substances: A Historical Perspective
The Effects of Drugs on Behavior Maintained by Social Contact: Role of Monoamines in Social Reinforcement
Dual action of ketamine confines addiction liability
Psychedelic Knowledge and Opinions in Psychiatrists at Two Professional Conferences: An Exploratory Survey
Regulation of human research with LSD in the United States (1949-1987)
Self-reported negative outcomes of psilocybin users: A quantitative textual analysis
Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review
Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs
Population pharmacokinetic/pharmacodynamic modelling of the psychedelic experience induced by N,N-dimethyltryptamine – implications for dose considerations
Separating the agony from ecstasy: R(-)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice
Harm potential of magic mushroom use: A review
Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines
The relationships of classic psychedelic use with criminal behavior in the United States adult population
Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species
Effects of Selective Serotonin Reuptake Inhibitor Use on 3,4-Methylenedioxymethamphetamine–Assisted Therapy for Posttraumatic Stress Disorder
Pharmacokinetics and pharmacodynamics of oral psilocybin administration in healthy participants
Psychedelic pleasures: An affective understanding of the joys of tripping
Motives for the use of serotonergic psychedelics: A systematic review
Remembering Molly: Immediate and delayed false memory formation after acute MDMA exposure
Bringing Ayahuasca to the Clinical Research Laboratory
Developing Guidelines and Competencies for the Training of Psychedelic Therapists
Flashbacks and HPPD: A Clinical-oriented Concise Review
Turn on, Tune in, and Drop out: Predictors of Attrition in a Prospective Observational Cohort Study on Psychedelic Use
Adverse effects of ayahuasca: Results from the Global Ayahuasca Survey
Does getting high hurt? Characterization of cases of LSD and psilocybin-containing mushroom exposures to national poison centers between 2000 and 2016
Adverse effects of psychedelics: From anecdotes and misinformation to systematic science
Side-effects associated with ketamine use in depression: a systematic review
Is psychedelic use associated with cancer?: Interrogating a half-century-old claim using contemporary population-level data
Human pharmacology of mephedrone in comparison with MDMA
Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose–effect study
Hallucinogen persisting perception disorder: what do we know after 50 years?
Psychedelics as a Training Experience for Psychedelic Therapists: Drawing on History to Inform Current Practice
Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review
Hallucinogen persisting perception disorder and the serotonergic system: A comprehensive review including new MDMA-related clinical cases
Interaction of Sex and Age on the Dissociative Effects of Ketamine Action in Young Healthy Participants
Migraine prevalence in visual snow with prior illicit drug use (Hallucinogen Persisting Perception Disorder) versus without
Psychedelics and the essential importance of context
Systematized Review of Psychotherapeutic Components of Psilocybin-Assisted Psychotherapy
Safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg LSD in healthy participants within a novel intervention paradigm: A proof-of-concept study
Optimizing outcomes in psilocybin therapy: Considerations in participant evaluation and preparation
Presence, Trust, and Empathy: Preferred Characteristics of Psychedelic Carers
‘Never drop without your significant other, cause that way lies ruin’: The boundary work of couples who use MDMA together.
Psilocybin use is associated with lowered odds of crime arrests in US adults: A replication and extension
Prediction of psilocybin response in healthy volunteers
Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition
Translating Psychedelic Therapies From Clinical Trials to Community Clinics: Building Bridges and Addressing Potential Challenges Ahead
Expert Opinion on Psychedelic-Assisted Psychotherapy for People with Psychotic Symptoms
Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences
Abnormal visual experiences in individuals with histories of hallucinogen use: A web-based questionnaire
Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants
Visitors of the Dutch drug checking services: Profile and drug use experience
Toxicities Associated With NBOMe Ingestion—A Novel Class of Potent Hallucinogens: A Review of the Literature
The association between naturalistic use of psychedelics and co-occurring substance use disorders
A retrospective analysis of the “Neverending Trip” after administration of a potent full agonist of 5-HT2A receptor – 25I-NBOMe
User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study
MDMA and memory, addiction, and depression: dose-effect analysis
The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability
Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey
Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial