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/

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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

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

On Perception and Consciousness in HPPD: A Systematic Review

Adverse Reactions to Psychedelic Drugs - A Review of the Literature

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

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?

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

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

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

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

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

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

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

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