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Psychedelics as Medicine: What Research Says About the Long-Term Effects

The study of psychedelics has entered a new era — changing laws and public opinion are fueling a fresh wave of research. These mind-altering substances, once known for their counterculture associations, are now being studied for their ability to help with tough-to-treat conditions like depression and anxiety. But what does science say about the long-term effects of psychedelics?

Understanding psychedelics

Psychedelics are a group of mind-altering substances that temporarily affect thinking, emotions, senses, and mood. Humans have used them for thousands of years for recreational, spiritual, and medicinal purposes. Psychedelics include drugs like psilocybin (magic mushrooms), lysergic acid (LSD or acid), ketamine, and DMT, the active chemical in ayahuasca.

Potential benefits of psychedelics

Psychedelics affect consciousness and perception, leading to an altered perspective that can recalibrate the mind, while neurochemical changes may alter brain function. It’s precisely these kinds of effects that make psychedelics promising targets for research in mental health.

There is a wave of emerging evidence that psychedelics can be a potent treatment option for hard-to-treat mental health conditions, such as depression, anxiety, and obsessive-compulsive disorder. A small-scale study published in Nature Scientific Reports even found that LSD and magic mushrooms may be associated with a boost in users’ sex lives and levels of sexual pleasure.

Yet, despite the growing body of evidence in their favor, substances like psilocybin and LSD remain controversial. Today, many preconceptions about the long-term effects of psychedelics and their safety persist, resulting from their classification as ‘drugs of abuse’ and negative media reports in the mid-20th century.

Long-term effects of psychedelics

Much of the research on the long-term effects of psychedelics has used small sample sizes, short follow-up periods, and different data collection methods. Because of these variations between studies, drawing firm conclusions about the long-term effects of psychedelics remains challenging.

A 2020 systematic review published in Neuroscience and Biobehavioral Reviews examined findings across dozens of studies to assess if changes in mood, behavior, social function, and physical health continue over the long term.

Positive long-term effects of medical and recreational use of psychedelics

While further research is necessary, some initial findings regarding psychedelic use in controlled environments and doses are promising.

Depression and anxiety

Depression and anxiety are among the most common mental health problems, and research into psychedelics as a treatment for these conditions is one of the fastest-growing areas. A 2023 systematic review and meta-analysis published in the Journal of Affective Disorders reported a reduction in depressive symptoms following the administration of psilocybin, LSD, or ayahuasca in combination with psychological support.

Significant depressive symptom alleviation was indicated up to 5 weeks later. However, the reviewers noted that any association between psychedelics and the reduction in depressive symptoms should be interpreted cautiously due to the small sample sizes and low number of studies.

A review of eight studies conducted in 2020 that examined the use of psychedelics in patients with anxiety found that seven of the studies showed a significant long-term reduction in symptoms.

Generally, the reviewers concluded that the positive effects of psychedelics remained over the long term. In some cases, depression and anxiety would relapse, but generally to levels below what they were before psychedelic treatment.

Personality changes

Several studies in the review found links between psychedelic treatment and lasting changes in personality and attitude. Openness to new experiences and increased sociability and extroversion were also linked to psychedelics. In a 2019 study, two doses of psilocybin therapy in a supported setting were associated with lower levels of neuroticism, which is typically linked to unpleasant feelings such as anxiety, worry, fear, and anger.

Researchers have suggested that these effects may be because psychedelics lead to changes in brain signaling and new connections between different parts of the brain that allow for new ways of thinking.

Social changes

Recent research has highlighted the transformative potential of psychedelics such as psilocybin and LSD in fostering positive social changes. These substances have been found to modify activity in the brain regions responsible for our sense of self. This same area, known as the default mode network (DMN), is also linked to mind wandering, introspection, and rumination. Researchers believe that modified activity in the DMN may enable a heightened sense of unity and selflessness.

A small-scale study of patients with treatment-resistant depression found that two doses of psilocybin a week apart were associated with lasting effects on relatedness to nature and decreased authoritarian political beliefs. Several studies have also linked controlled psychedelic use to altruism and improved social relations. This may be because psychedelics have been noted to increase levels of oxytocin, commonly known as the ‘love hormone,’ which is associated with social behaviors with altruism, cooperation, caring for others, and trust.

Drug use and criminality

Contrary to conventional beliefs linking drug use to criminality, several pieces of research have linked the recreational use of psychedelics to a reduction in antisocial and criminal behavior. A 2017 study looking at the social effects linked to psychedelics surveyed over 40,000 illicit opioid users and found that recreational psychedelic use was associated with a 40% reduction in opiate abuse in the past year.

A separate study of over 25,000 individuals in the community correction system also found that recreational psychedelic use was associated with a 40% reduction in the risk of drug and alcohol use, leading to prison recidivism, with researchers suggesting that hallucinogens may promote drug abstinence and pro-social behavior. Other research into psychedelics and emotional regulation reported that males reporting one or more episodes of psilocybin or LSD use in their lifetime were nearly 60% less likely to commit acts of domestic violence.

Spiritual and personal growth

Some of the most marked effects of psychedelics take place in spiritually active people, meaning they take part in religious or spiritual events and activities. In one study, 79% of spiritually active people reported increased well-being and feelings of life satisfaction up to two months after a single psilocybin session.

These spiritual findings have been noted in studies of patients experiencing terminal and life-threatening illnesses, such as cancer. Two randomized control trials from 2016 and 2018 found that the use of psilocybin in a controlled setting was associated with increased measures of satisfaction and well-being as well as increased appreciation of life and comfort around thoughts of death and dying in over 80% of patients.

Enhanced creativity

In a 1967 study, a single 200 microgram dose of LSD was associated with an enhanced appreciation of culture, music, and art up to six months later. People reported that they had bought more records, spent more time in museums, and been to more live music events than the control subjects who were given either amphetamine or low-dose LSD. More recent studies have supported these findings.

A contemporary study from the Journal of Psychoactive Drugs aimed to examine the longer-term effects of psilocybin on measures of creativity in 50 attendees of a psilocybin retreat. Researchers found that 44% of attendees had increased measures of creative thinking one week after a single dose, although the size of the study meant that this wasn’t statistically significant. Similarly, a 2018 study of ayahuasca retreat participants found that measures of creative thinking were significantly increased a month after an ayahuasca retreat.

Negative long-term effects of medical and recreational use of psychedelics

A 2022 review in the Journal of Psychopharmacology aimed to look at the evidence for potential harm caused by psychedelics. The reviewers found that many of the negative perceptions surrounding psychedelics were unsupported by evidence.

Psychological changes, mental health problems, and psychosis

The risk of psychological changes such as psychosis or chronic mental health problems is a common fear, however, these are extremely rare. In one survey of 1,993 people who had experienced a challenging psychedelic experience, only 0.15% had prolonged or distressing psychotic symptoms.

A large-scale population study of 130,000 U.S. adults found no association between psychedelic use and mental health problems, such as suicidal thoughts, depression, and anxiety. Users were less likely to have required mental health treatment in the past year.

In these studies, thorough psychiatric screening of patients with a predisposition toward psychotic illnesses has meant that no psychotic episodes have been documented in modern clinical trials.

Physical risks and risks of death

Other concerns around psychedelics are that they are toxic to the body and can lead to brain damage. Many studies that drew these conclusions have been challenged. A large body of modern research has found that psychedelics are physiologically safe, and no long-term neurocognitive deficits have been reported by participants in the modern era of psychedelic research. Psychedelics can, however, cause temporary increases in heart rate, blood pressure, and body temperature and should be used with caution in those with physical health conditions, such as heart disease.

A 2022 review of the adverse effects of psychedelics in research found that the risks of death due to psychedelics are low, and when they have been reported in research, occurred when higher doses are used or when other substances are involved. Mortality is more common in patients with physical or mental health disorders, such as acute asthma and manic-depressive illness, and when psychedelics are used in unsupervised settings.

However, a survey conducted by the Substance Abuse and Mental Health Services Administration in the U.S. found that even in uncontrolled settings, fewer than 1% of LSD and psilocybin users seek medical assistance, and ‘hallucinogens’ are responsible for 0.1% of hospital admissions, which ranks them far below other recreational drugs and substances such as alcohol.

Dependency and misuse

While all drugs carry some potential for abuse, the risk in psychedelics is low, and multiple studies have found that the risk of dependency, addiction, abuse, and misuse is low. LSD and psilocybin have been ranked below all other recreational drugs in terms of rate of abuse and dependency risk, and even active, ritual users of ayahuasca do not experience the same negative psychosocial effects linked to other drugs of abuse.

Last word

Psychedelics are a promising frontier for mental health treatment, with the potential for sustained improvements in a range of conditions from depression to anxiety. Their use, however, comes with a firm caveat — their responsible use in clinical or controlled settings. The path forward calls for robust research with an emphasis on long-term safety and effectiveness.


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