Drugs and Substances: Learn It 5—Hallucinogens

Hallucinogens

hallucinogens

Hallucinogens are a diverse class of drugs that induce significant changes in sensory perception and cognitive experiences. These alterations can manifest as visual or auditory hallucinations, distorted body sensations, and a skewed sense of time. Some well-known hallucinogens include psilocybin (commonly known as “shrooms”), mescaline (found in peyote), and LSD (lysergic acid diethylamide). These are sometimes called psychedelic or dissociative drugs.

Common examples

  • Classic psychedelics: Psilocybin (in “magic mushrooms”), LSD (lysergic acid diethylamide), Mescaline (from peyote cactus)

  • Dissociatives: Ketamine and PCP (“angel dust”)

    These act on different neural systems—classic psychedelics often act via serotonin (5-HT2A) receptors, while dissociatives act more via NMDA glutamate receptor antagonism.

How they work in the brain

  • Classic psychedelics (LSD, psilocybin, mescaline) function primarily as serotonin 5-HT2A receptor agonists, altering sensory and perceptual processing.

  • Dissociatives (ketamine, PCP) block or modify the action of NMDA glutamate receptors, which can fragment normal consciousness, change body-awareness, and affect memory.

Because their effects are more about perception and cognition than about intense reward or relief of negative states, hallucinogens are generally seen as less physically addictive than stimulants or opioids—but that doesn’t mean they’re risk-free.

An illustration shows a colorful spiral pattern.
Figure 1. Psychedelic images like this are often associated with hallucinogenic compounds. (credit: modification of work by “new 1lluminati”/Flickr)

cannabis

Cannabis, also known as marijuana, is often grouped with hallucinogens, but it’s essential to note that its effects are more varied and can include features of stimulants and depressants. It is not officially classified as a hallucinogen. The active compound in marijuana, THC (tetrahydrocannabinol), interacts with the endocannabinoid system in the brain, affecting mood, perception, and appetite

Understanding Marijuana

Marijuana has various mental and physical effects, which include euphoria, relaxation, altered states of mind and sense of time, difficulty concentrating, impaired short-term memory, impaired body movement (balance and fine psychomotor control), and an increase in appetite. The onset of effects is felt within minutes when smoked, but may take up to 90 minutes when eaten. The effects usually last for two to six hours, depending on the amount used. Physical effects may include dry mouth, red eyes, increased heart rate, difficulty breathing, or nausea. At high doses, mental effects can include anxiety, delusions (including ideas of reference), hallucinations, panic, paranoia, and psychosis.

While many argue that marijuana is not as harmful as other commonly abused drugs, it is still a mind-altering substance that comes with risk. Though it is not as addictive as nicotine, 30% percent of marijuana users are likely to develop a dependency on the drug.[1] There is also a strong relation between cannabis use and the risk of psychosis, though the direction of causality is debated. Other long-term adverse effects may include decreased mental ability in those who started regular use as adolescents, chronic coughing, susceptibility to respiratory infections, and cannabinoid hyperemesis syndrome.

Medical Marijuana

As of 2025, medical marijuana remains in a state of regulatory flux. While medical marijuana is legal in most U.S. states and recreational use is permitted in several, federal law continues to classify marijuana as an illegal Schedule I substance. This classification has traditionally indicated substances with no accepted medical use and high abuse potential.

A photograph shows a window with a neon sign. The sign includes the word “medical” above the shape of a marijuana leaf.
Figure 2. Marijuana can be used for medical reasons, but its best usage and dosing is still being researched (credit: Laurie Avocado).

However, significant policy changes are underway. In May 2024, the Drug Enforcement Administration (DEA) proposed rescheduling marijuana from Schedule I to Schedule III—a classification reserved for substances with accepted medical uses and lower abuse potential. This proposal underwent public comment and hearings in late 2024, though marijuana remains Schedule I as the rescheduling process continues into 2025. The disconnect between state and federal law complicates both patient access and scientific research.

Medical marijuana is prescribed for various health conditions. Common medical uses include stimulating appetite in chemotherapy patients experiencing treatment-related weight loss, managing chronic pain, treating muscle spasms, and addressing anxiety and depression.

Recent research has provided mixed but often encouraging findings about marijuana’s therapeutic effects. A 2024 longitudinal study from the University of Melbourne found that patients using prescribed medical cannabis reported significant improvements in chronic pain during the first six months of treatment, with sustained benefits in depression, anxiety, and sleep problems over a full year (Halman et al., 2024).[2] Similarly, a 2020 observational study tracking patients over 12 months found improvements in pain severity and interference, along with better physical and mental health outcomes (Safakish et al., 2020).[3]

Patients in both studies also reported reducing their use of other pain medications, including opioids. However, the evidence remains complex. While survey data from Florida’s medical cannabis program showed that over 95% of patients reported improvements in anxiety and chronic pain (Medical Cannabis and Cannabinoids, 2024), the Centers for Disease Control notes that scientific evidence supporting cannabis for most types of chronic pain remains limited, with the strongest support for neuropathic pain specifically.

Emerging Psychedelic-Assisted Therapies

Scientists are exploring how certain psychoactive drugs, combined with psychotherapy, might help treat mental health conditions. This growing field—called psychedelic-assisted therapy—revived in the 2010s after decades of research restrictions under the 1970 Controlled Substances Act.

Two of the best-known substances being studied are psilocybin (from certain mushrooms) and MDMA (often known as ecstasy). Both have received “breakthrough therapy” status from the FDA for potential use in mental health treatment—psilocybin for depression and MDMA for post-traumatic stress disorder (PTSD).[4]

Early studies suggest that, when used in carefully controlled settings with professional therapy, these drugs can reduce symptoms for some people. However, research is still limited, and in 2024 the FDA decided that more large-scale trials are needed before approving MDMA-assisted therapy for PTSD.

Ketamine for Depression

Ketamine, a long-used anesthetic, can produce rapid relief from depression symptoms—sometimes within hours. A related drug, esketamine, was approved by the FDA in 2019 as a nasal spray for treatment-resistant depression. Roughly one-quarter to one-half of patients respond, though the effects often fade without follow-up doses. Common side effects include short-term dissociation, nausea, and raised blood pressure.[5]

These treatments remain experimental. Most require intensive therapy sessions, medical supervision, and specially trained professionals. Except for ketamine, the drugs are still Schedule I controlled substances, which limits research and clinical access.

Summary of Psychoactive Drugs

Substance use disorder is defined in DSM-5 as a compulsive pattern of drug use that persists in spite of negative consequences. Both physical and psychological dependence are often involved with this disorder.

  • Alcohol, barbiturates, and benzodiazepines are central nervous system depressants that affect GABA neurotransmission.
  • Cocaine, amphetamine, cathinones, and MDMA are all central nervous stimulants that agonize dopamine neurotransmission, while nicotine and caffeine affect acetylcholine and adenosine, respectively.
  • Opiate drugs serve as powerful analgesics through their effects on the endogenous opioid neurotransmitter system.
  • Hallucinogenic drugs cause pronounced changes in sensory and perceptual experiences and vary with regard to the specific neurotransmitter systems they affect.
Visit the Mouse Party website to see a visual example of how drugs alter the chemicals in the brain.
  1. NIDA. 2021, April 13. Is marijuana addictive? Retrieved from https://nida.nih.gov/publications/research-reports/marijuana/marijuana-addictive on 2023, October 17 ↵
  2. Halman, A., Chenhall, R., & Perkins, D. (2024). Changes in pain and mental health symptoms associated with prescribed medicinal cannabis use: A one-year longitudinal study. Journal of Pain and Palliative Care Pharmacotherapy, 39(1), 38-50. https://doi.org/10.1080/15360288.2024.2414898 ↵
  3. Safakish, R., Ko, G., Salimpour, V., Hendin, B., Sohanpal, I., Loheswaran, G., & Yoon, S. Y. R. (2020). Medical cannabis for the management of pain and quality of life in chronic pain patients: A prospective observational study. Pain Medicine, 21(11), 3073-3086. https://doi.org/10.1093/pm/pnaa163 ↵
  4. National Institute of Mental Health. (2024). Psychedelic-assisted therapy for PTSD. PTSD: National Center for PTSD. https://www.ptsd.va.gov/professional/treat/txessentials/psychedelics_assisted_therapy.asp ↵
  5. Yavi, M., Lee, H., Henter, I. D., Park, L. T., & Zarate, C. A. (2022). Ketamine treatment for depression: A review. Discover Mental Health, 2, 9. https://doi.org/10.1007/s44192-022-00012-3 ↵