Hallucinogens and Their Therapeutic Use : A Literature Review, Matthew J. BEGOLA, Jason E. SCHILLERSTROM,2019

Hallucinogens and Their Therapeutic Use : A Literature Review


Journal of Psychiatric Practice, 2019, 25, (5), 334–346

Doi : 10.1097/PRA.0000000000000409


The exploration of possible therapeutic benefitsof hallucinogenic substances has undergone a revitalization in the past decade. This literature review investigated the published literature regarding the psychotherapeutic uses of hallucinogens in psychiatric disorders. The results showed that a variety of substances have been evaluated in the treatment of psychiatric disorders, including ayahuasca, ibogaine, ketamine, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, and psilocybin. The conditions treated ranged from depression to autism, with the largest volume of research dedicated to substance use disorders. The majority of studies that were reviewed demonstrated significant associations with improvement in the conditions investigated. However, it was difficult to draw definitive
conclusions as most studies suffered from small sample sizes, inconsistent measures, and poor study design. To properly assess the risks and potential benefits of hallucinogens in psychiatric treatment, there is a need for well designed, standardized studies that demonstrate the impact of hallucinogenic substances on psychiatric conditions.

KEY WORDS : hallucinogens, hallucinogenic drugs, psychedelics, psychiatry, lysergic acid diethylamide (LSD), psilocybin, ibogaine, ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), ketamine

Hallucinogens are classified by the fifth edition of the American Psychiatric Association’s Diagnostic
and Statistical Manual of Mental Disorders (DSM-5) as a diverse group of substances that, despite having different chemical structures and possibly involving different molecular mechanisms, produce similar alterations of perception, mood, and cognition in users.1 Multiple substances comprise this category ranging from naturally occurring plants to synthetically produced compounds. Examples include ayahuasca, ibogaine, ketamine, lysergic acid diethylamide (LSD), 3,4 methylenedioxymeth-amphetamine (MDMA), and psilocybin (the active ingredient in “magic mushrooms”).

Although hallucinogens have been used in spiritual rituals among multiple cultures for nearly 2500 years, they were largely unknown to western society until the discovery of LSD’s mind altering effects in 1943.2 In 1947, the first clinical paper published about LSD discussed possible applications in the field of
psychiatry.2 Subsequently, LSD was sold under the name Delysid. The first indication listed in its information packet was “analytical psychotherapy, to elicit release of repressed material and provide mental relaxation, particularly in anxiety states and obsessional neuroses.”2 Although now disproven, the second indication encouraged self-experimentation to perform studies on the nature of psychoses, advising “by taking Delysid himself, the psychiatrist is able to gain an insight into the world of ideas and sensations of mental patients.”2 Research with psychedelics occurred for 2 decades until widespread misuse, political pressures, stigmatization, and eventual illegalization ended the investigations. However, these same adverse factors that stopped academic research have not curtailed illicit exploration and abuse.

The 2015 National Survey on Drug Use and Health estimates that > 40 million people (15.3% of the US population) have used hallucinogens at least once in their lifetime.3 Given increasingly lax substance control laws, the increasing availability of hallucinogenic substances on the Internet, and travel to experience ritualistic hallucinogenic use becoming more frequent,4 the number of hallucinogenic users is predicted to increase. These factors make psychiatrists’ knowledge about hallucinogens more than a matter of academic curiosity, but rather valuable in daily patient management. After decades of obscurity, the field of psychedelic research is reemerging. In 2012, the University of Pennsylvania hosted “Psychedemia,” a weekend event attended by researchers, clinicians, and other scientists to discuss the impact of hallucinogens in a variety of fields.5 In April 2017, the largest reported gathering of professionals to discuss hallucinogenic research took place in California, boasting an
attendance of 3000.6 Most recently, in September 2017, the United States Food and Drug Administration (FDA) approved a phase 3 trial for MDMA-assisted psychotherapy for patients with posttraumatic stress disorder (PTSD).7 Despite increasing awareness of and revitalized interest in hallucinogens, their safety and usefulness have been debated and challenged in the medical literature.8–10

While the use of hallucinogens remains controversial, investigation of clinical applications of illicit substances is not a novel idea. Many illicit substances are classified by the FDA to allow their use in specific clinical scenarios. Examples include the use of cocaine for nose bleeds and anesthetic eye
drops, opioids for pain, and cannabinoids for pain, glaucoma, and appetite stimulation. Hallucinogens
are unique, however, as their therapeutic use is believed to go beyond their physiological actions, many of which are just beginning to be discovered. Rather, the therapeutic value of hallucinogens is attributed to their distinct ability to alter consciousness and invoke new insights, thereby creating fundamental changes in mental schema.11,12 While some argue that one experience cannot produce life changing effects, research has shown at 14 months after receiving a psychedelic dose of psilocybin, 50% of subjects rated the experience as “the most personally meaningful and spiritually significant of their lives,” with 64% reporting “increased well-being or life satisfaction.”13



This review includes ayahuasca, dipropyltryptamine (DPT), diethyltryptamine (DET), ibogaine, ketamine, LSD, MDMA, and psilocybin. All of these substances possess hallucinogenic properties, but their mechanisms of action and proposed therapeutic attributes vary.