First LSD Study In 35 Years Treats Last SubjectAccording to MAPS, on May 26, 2011, the last subject was treated in a study of LSD-assisted psychotherapy for anxiety due to life-threatening illness.  This study is the first clinical LSD study to take place in over 35 years.

The study was led by psychiatrist Peter Gasser, M.D., who has stated that he feels that the treatment used in the study helped subjects to overcome feelings of despair and isolation that can come along with confronting death. He further reported that subjects seemed to be able to open up and reconnect with the world in unexpected and powerful ways when working with LSD.  Furthermore, not a single subject is reported to have had a serious negative reaction to the treatment, which is truly remarkable (Gasser 2007).

In a recent talk at the 2011 MAPS conference, the principle investigator for the study, Peter Gasser, stated that the final results of the study are as yet not fully compiled.  According to currently available data, LSD does seem to have significantly improved quality of life scores for individuals with end of life anxiety, and also created a positive trend in reducing anxiety in patients.  However, it is important to keep in mind that this was a pilot study with only 12 subjects.  The purpose of such a pilot study is not to obtain significant statistics, but to figure out the best protocol for carrying out an innovative experiment such as this one.  Of more interest than the statistical data is the fact that so many of the patients who received LSD-assisted psychotherapy reported extremely powerful and positive experiences and expressed their desire to continue such therapy in the future.

Concerning LSD

LSD is a psychoactive substance which causes direct activation of serotonin, dopamine and norepinephrine receptors.  It seems that its hallucinogenic effects are due to the fact that LSD is a 5HT2A agonist – that is, it increases the activity of the 5HT2A serotonin receptor sites in the brain.  LSD has extremely low toxicity – the LD50 in humans may be estimated to be about 0.2 mg/kg, or about 14,000 mcg/kg.  In simple words, this means that 50% of individuals who take 14,000 mcg of LSD per kg of body weight will die.  Given the fact that average doses of LSD used in previous human research have been between 25-500 mcg PER PERSON, we can see that LSD, especially in a controlled research study setting, is a remarkably physically safe substance (Jerome 2008).

LSD tends to increase blood pressure and heart rate as well as body temperature and blood glucose levels, but does not tend to do so consistently or significantly.  A dose of LSD will begin to affect a subject 30-90 minutes after administration, with effects lasting 5-10 hours.  Effects generally peak within the first 2-4 hours.  Effects can vary widely across individuals and across various settings, and include extreme mood changes, visual distortions, alterations in perception of time, depersonalization and an altered sense of reality.  Higher doses often seem to produce a transcendent experience.  Psychedelic doses of LSD seem to impair performance on working memory tasks such as word recall, and increase creative responses and ability.

LSD is not associated with disease or damage to any organ or body system.  There is a complete lack of case reports of physical adverse effects of using the substance, and given the 40-50 years of medical and non-medical use of the substance, this is remarkable.  Only two fatalities have ever been linked directly to LSD, and due to a lack of detailed information regarding these cases, it is hard to tell if the deaths were actually directly attributable to LSD.

Adverse side effects, therefore, are almost completely psychological and include anxiety, panic and psychotic reactions.  These effects are transient, lasting no longer than the 8-10 hour duration of the substance.  Individuals who take LSD may also sometimes engage in reckless behavior, such as driving under the influence, but this sort of behavior can easily be controlled by keeping study participants in the clinic during the effects of the substance.  The most serious known side effect of LSD use is that some few individuals will enter transient psychotic states after LSD use.  Strassman has suggested that PSD may trigger psychotic episodes in people who are already prone to psychosis.  One study found that .08% of 5000 volunteers in a study reported having psychotic or panic reactions that lasted for more than two days.  The rate was slightly higher in individuals who were psychiatric patients.  So, while LSD can indeed provoke psychosis in a very small number of people, it does not do so very often.  The occurrence of transient psychosis may also be reduced further by screening subjects for mental health and excluding individuals with past or current psychotic disorders or first-degree relatives with such disorders (Jerome 2008).

Despite the fact that LSD has been shown repeatedly in studies to have little to no abuse liability, it is placed in US Schedule 1, defined as having no medical use and high abuse liability, and it is treated internationally as a controlled substance. During the 1950’s and 60’s, thousands of individuals received LSD in the context of psychological research studies.  However, due to increased legal restrictions of the substance, no new human LSD studies have been published in the last two decades.  The original trials indicate that LSD can be administered safely in a research study.  Furthermore, LSD was found to reduce depression, anxiety and social isolation in alcoholics when combined with psychotherapy (Kurland et al. 1971), and was also found in several other studies to reduce anxiety in individuals with advanced stage cancer.  As an example, 36% of subjects with advanced stage cancer given 200-500 mcg LSD and treated with psychotherapy reported moderate improvement in emotional distress, and 36% reported dramatic improvement (Kurland 1973).  It has also been suggested that LSD may be an effective treatment for breaking cluster headache cycles, and although there are not presently any controlled studies available regarding this, there are plans to conduct studies in to this application of the substance.

Due to all of the above, it is clear that LSD is not only incredibly safe, particularly in a research setting, but that it may have great potential for treating anxiety, depression and for assisting individuals who are preparing for the death process.  Therefore, it is very exciting to see that the first stage of the LSD-assisted psychotherapy study for individuals with advanced stage illness has been completed.

Concerning the MAPS Study

The MAPS study is an active-placebo controlled investigation into the therapeutic usage of LSD-assisted therapy for individuals “confronting anxiety related to advanced-stage illnesses”.  Eight of twelve participants were assigned to the active dosage of 200 mcg LSD, while 4 of the twelve were assigned to the low dose active placebo of 20 mcg LSD.  Participants received two sessions of LSD-assisted psychotherapy separated by a two to four week interval and imbedded in a course of 6-8 non-LSD therapy sessions for purposes of preparing for and integrating the LSD-assisted therapy sessions.  Anxiety levels, quality of life and pain were assessed and recorded throughout the study (Gasser 2007).

The purpose of the study is to evaluated the therapeutic potential of LSD-assisted therapy and to eventually develop a way in which licensed psychiatrists and psychologists can utilize LSD legally as part of treatment. The study is seeking to determine if LSD can be safely administered to patients without adverse events, if participants who receive LSD-assisted therapy will experience a decrease in anxiety both after the session and over a two month period, and if participants will experience an improvement in quality of life lasting up to follow-ups two months after the second session.

Clinical research and anecdotal reports of LSD use has suggested that LSD may be an effective treatment for the psychological distress that can follow an individual being diagnosed with a life threatening illness.  LSD is reported to create a change in the perception of the self and the world, “including ego dissolution, feelings of transcendence or transformation, and increased and decreased distress that may assist people in facing and grappling with physical deterioration and impending death” (Gasser 2007).  Therefore, it may be able to assist individuals who are dealing with the death process, and may also help to decrease the need for anxiolytic agents such as benzodiazepines, which are very addictive and have serious long term effects on quality of life.

More information on the MAPS study in to LSD-assisted therapy for individuals facing life-threatening illness, including the full study protocol.

It will be fascinating to see the full results of this study, and, given comments that Dr. Gasser has already made, it seems as if the results will be overwhelmingly positive.  It is exciting to know that medicines such as LSD and other psychoactives are again being considered and researched for their potential uses in the field of psychiatry, and it seems that this trend is only going to continue growing with the work of organizations such as MAPS.  MAPS is conducting or planning to conduct research in to psychedelics in six countries on four continents.  They are planning for studies of ibogaine treatment of addiction in New Zealand, and just finalized data in a Swiss study of MDMA-assisted psychotherapy for PTSD, among other endeavors.

 

REFERENCES

Gasser, P. LSD-assisted psychotherapy in persons suffering from anxiety associated with advanced-stage life threatening diseases.  A phase-II, double-blind, placebo-controlled dose-response pilot study. MAPS, 2007.
Jerome, L. “D-Lysergic Acid Diethylamide (LSD): Investigator’s Brochure”. MAPS, 2008.
Kurland, A.A, C. Savage, W.N. Pahnke, S. Grof, and J.E. Olsson. “LSD in the treatment of alcoholics.” Pharmakopsychiatrie, Neuro-Psychopharmakologie 4, no. 2 (1971): 83-94.
Kurland, A.A., S. Grof, W.N. Pahnke, and L.E. Goodman. “Psychedelic Drug Assisted Psychotherapy In Patients with Terminal Cancer.” In Psychotheramacological Agents for the Terminally Ill and Bereaved, edited by I.K. Goldberger, S Malitz, and A.H.
Kutscher, 86-133. New York, NY: Columbia University Press, 1973.