LSD and Managing Mental Health

The History of LSD and Managing Mental Health

Since the discovery of Lysergic acid diethylamide’s (LSD) in 1938 by Swiss chemist Albert Hoffman, using the terms LSD and managing mental health in the same sentence has been met with a combination of skepticism, enthusiasm and outrage.  The lack of consistency in research limits studies’ ability to find a definite effect of LSD.

The History of LSD

LSD and Managing Mental Health
Albert Hoffman, the scientist who discovered LSD.

Not originally thought of as a psychiatric treatment, LSD was synthesized from ergot derivatives as a medication to reduce postpartum hemorrhage, with Hoffman first experiencing its hallucinogenic effects after accidentally dosing himself. Marketed by Sandoz, Hoffman’s employer at the time, under the brand name “Delysid” in the 1950s,  interest among psychiatrist evolved in the potential use of LSD as a therapeutic agent and the substance was used in several psychiatric departments in Europe and America.  In the late 1950s, even prominent US celebrities like  Cary Grant and Esther Williams took LSD under the guidance of Dr. Mortimer Hartman at the Psychiatric Institute of Beverly Hills in order to manage their states of mind.

Studied from the 50s to 70s, even after its federal prohibition in the US,  to evaluate LSD induced behavioral and personality changes.  LSD was used in the treatment of:

LSD and Managing Mental Health
Screen legend Cary Grant.
  • Anxiety
  • Depression
  • Psychosomatic diseases
  • Addiction

The study of LSD as a treatment for mental health problems came to a grounding halt due to:

  • Increasing recreational use.
  • Safety concerns
  • Scheduling restrictions.
  • US Army and CIA MK-Ultra experiments with LSD

As a result of these factors, most studies were not performed with proper research protocols and standards, further tainted the reputation of the drug.  This lead to studies been viewed with skepticisms from mainstream medicine, and it has taken several decades for research in LSD therapeutic potential to recover.  After US prohibition in 1967 as result of popularity in counter-cultural movements, it has taken several decades for a resurgence of interest in its therapeutic potential for psychiatry.  Recent years have seen an increased interest in ‘psychedelics’ as potential psychiatric treatments. There have been some promising results in pilot studies administering psychedelic drugs to patients with “treatment-resistant” mental illness

Research into LSD and Managing Mental Health

How LSD May Help Understand Mental Disorders

LSD molecule
Structural formula of LSD

Certain mental disorders, like schizophrenia and depression, are characterized for impairing an individual’s sense of self, making it difficult for people to distinguish themselves from others,  impairing everyday mental tasks and social interactions.  With regards to a dysfunctional sense of self:

  • Schizophrenics lose track of themselves.
  • Depressed people ruminate on themselves, stuck in an obsessive, self-oriented patterns of thought.

Understanding LSD’s ability to breaks down one’s sense of self may help researches experience symptoms of the disorders first and and find targets for future experimental drugs.  Animal studies suggested that 5-HT2 plays a role in LSD’s ability to alter one’s sense of self that blocking the receptor in humans might somewhat reduce the effect of LSD.  Research that used ketanserin (a 5-HT2 antagonist) to block the effect of LSD showed no difference between the performance of subjects who took LSD and ketanserin and a placebo group on measures of sense of self, indicating that 5-HT2 plays an important role in regulating sense of self in the brain.  Researchers indicate that the next step involve on drugs that target the 5-HT2 receptor to determine if they alleviate the symptomatology of psychiatric illnesses affecting the sense of self.

Therapeutic Effects of LSD

Early studies from the 1950s to 1970s indicated that LSD may have anti-depressive and anxiolytic (anti-anxiety) properties.  In the late 60’s/early 70’s LSD-assisted psychotherapy  was used in patients with:

  • Anxiety and cancer
  • Depression or related disorders

The reality was these studies, although held up by some as clear indication of the utility of LSD,  suffered from both poor documentation and  methodologies.  Additionally, different and mostly non-evidence-based therapies have been used in psychedelic-assisted therapy trials making comparisons between studies difficult.

Recent scientific literature reviews of randomized controlled trials (RCTs) testing the efficacy of LSD as a psychiatric treatment have been challenging.  One author screened 43 studies, published between 1966 and 2014 and found that only 11 (and 5 out of 11 had a high risk of bias related to participant and personnel blinding) were methodologically rigorous enough to be included in a scientific review; Many studies were excluded because:

  • They did not have a control group
  • Did not randomize participants.

In the studies that were included, shortcomings including:

  • Variation in drug dosing and control:
    • There was huge variation in the amount of LSD given (20 – 800 mcg of LSD administered to 567 patients.)
    • There were 404 control participants.
      • 7 studies used an active control (an alternative psychoactive drug or a lower LSD dose) .
      • 4 studies had a control group who received no drug.
  • Variation in set and setting:
    • In 4 of the studies, patient preparation ranged from brief orientation to more extensive preparation, aimed to promote the therapeutic experience.
    • During the LSD session, 5 studies delivered psychotherapy, while others commented on using a comfortable physical environment.
    • 2 of the studies included ‘integration’ sessions where participants discussed the LSD experience with a therapist.

Controlled LSD delivering within a therapeutic setting appears to be safe with the potential to be an effective treatment for some mental illness.

Efficacy of LSD

In the last 10 years, research in to LSD and managing mental health resurgences; first in healthy volunteers, but then in mental health patients. A meta-analysis of studies found LSD to be effective in managing substance abuse while another literature review concluded that LSD deserved further investigation as a treatment for mood disorders.

LSD and the Management of Mood Disorders

One modern trial evaluated the effects of LSD-assisted psychotherapy on anxiety in patients with life-threatening diseases.  At the beginning of the study:

  • All of the patients presented higher ratings of anxiety on standardized anxiety test,
  • Six were diagnosed with generalized anxiety disorder, and
  • Seven were diagnosed with major depression.

The study found:

  • A significant decrease in anxiety 2 months after the two LSD sessions compared with baseline anxiety scores.
  • Non-significant decreases in depression and increases in quality of life
  • That at 12 months post study,  nine patients reported:
    • sustained decreases in anxiety,
    • an increase in quality of life, and
    • no lasting adverse reactions after LSD.
  • No drug-related severe adverse effects were reported, with no panic reactions or other medical or psychiatric complications.

LSD and the Management of Substance Abuse

  • 3 studies of LSD in the management of alcohol use disorder found a significant effect of LSD on abstinence or drinking behaviour.
    • For two studies this was sustained at 6-12 months and for one study only up to 2 months.
    • One study found general health to improve in the LSD group, but no effect on alcohol use.
  • The study that tested LSD for heroin use disorder found a significant effect of LSD on abstinence rates at 12 months.

Over all, LSD may be effective in increasing abstinence from alcohol and heroin use disorders, and in reducing anxiety associated with life-threatening diseases.

LSD and Cluster Headaches

Single or few doses of LSD also reportedly lessened cluster headache and induced remission more effectively than conventional medications and researchers in Switzerland are in the beginning stages of a 3o patient study o investigate the effects of an oral LSD pulse regimen (3 x 100 µg LSD in three weeks) in cluster headache patients.

The Importance of Set and Setting in LSD Treatment

While many of the LSD trials  pay attention to patient preparation and aftercare, there was no consistent approach amongst, However given the the low rate of adverse events, regardless of the amount of preparation or dose size, suggests that it is worth researching the mount of preparation and psychotherapy is essential.

More so than with other psychiatric drugs, the context in which psychedelic drugs are administered, also referred to as ‘set’ and ‘setting’, is important.

  • ‘Set’ refers to a participant’s thoughts and expectations. In clinical use, this may involve psychotherapy to prepare the participant.
  • ‘Setting’ refers to the physical environment where people receive the drug; a comfortable room, music, the presence of supporters during the session. Other considerations are about including post-drug integration sessions.

As pointed out by numerous researchers, is not clear as to the amount of psychological support is sufficient to proved patients with the right “set” and in fact, new research into LSD is costly and time-consuming, in part due to the drug scheduling restrictions and the psychological support element.


As can be gleaned from the above, it is clear that the path forward for LSD as a tool for managing mental health relies on conducting more high quality research studies, but the initial work indicates that LSD is a low risk modality worth exploring.

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Amanda Smith

About the Author

I've battled depression for most of my adult life, so I speak with the voice and experience of someone who understands the fight.

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