A growing body of evidence suggests that LSD, psilocybin, and other hallucinogenic drugs may have therapeutic benefits for patients with psychiatric disorders, according to a research review in the September issue of Journal of Psychiatric Practice. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Hallucinogenic drugs have been studied for use in treating a wide range of psychiatric diagnoses, with nearly all of the studies reporting positive effects, concludes the review by Matthew J. Begola, DO, and Jason E. Schillerstrom, MD, of University of Texas Health Science Center at San Antonio

Hallucinogens for psychiatric disorders—what's the evidence?

When first developed in the 1940s, LSD (lysergic acid diethylamide) was viewed as a potentially useful drug for "analytical psychotherapy." Over the past decade, there has been a resurgence of interest in LSD and other hallucinogenic drugs for treatment of psychiatric disorders.

While the use of these drugs in psychiatry remains controversial, the use of illicit substances in specific clinical indications is not a new idea—as illustrated by the rapidly growing use of medical marijuana and cannabis derivatives. Drs. Begola and Schillerstrom write, "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."

A review of the research literature identified 16 studies of hallucinogenic drugs for treatment of psychiatric disorders. The studies addressed diagnoses ranging from depression to autism, and most commonly substance use disorders.

All but one of the studies reported that hallucinogens—used alone or as part of "augmentation" therapy"—produced clinically significant improvement in less time than commonly observed with traditional psychopharmacology or therapy," the researchers write. In most studies, side effects were manageable.

Four articles evaluated LSD to treat problems such as alcohol use disorder, anxiety, and schizophrenia. In the alcohol studies, LSD provided patients with increased insight into their problems, a sense of having "a new lease on life," and a stronger resolution to stop drinking. In one study, a single dose of LSD produced improvement lasting six months.

Psilocybin—best known as the hallucinogenic component of "magic mushrooms"—showed therapeutic benefits in three studies, including reduced anxiety and depression in patients with cancer and lasting improvement in symptoms of obsessive-compulsive disorder. Three studies of the anesthesia drug ketamine reported positive effects in patients with opioid use disorder, depression, and alcohol use disorder.

Other hallucinogenic drugs showing psychotherapeutic benefits included ayahuasca, an Amazonian botanical brew; ibogaine, a psychoactive alkaloid drug; and the synthetic drug MDMA (3,4-methylenedioxy-methamphetamine), commonly called "ecstasy." The FDA recently approved a phase 3 clinical trial of MDMA-assisted psychotherapy for post-traumatic stress disorder.

The authors note that the studies had some important limitations—such as small sample size, inconsistent measures, and poor research design—which make it difficult to draw definitive conclusions. They emphasize the importance of carrying out higher-quality, longer-term studies, especially careful randomized controlled trials, before these drugs can be recommended or approved for therapeutic use.

"Despite promising findings in therapeutic hallucinogen trials, current factors, including funding, laws, and stigma, continue to impose limitations on further research," Drs. Begola and Schillerstrom add. "At some point, the field must overcome these barriers if we are to advance our knowledge about the impact of hallucinogenic agents on the treatment of serious mental conditions."