The powerful hallucinogen LSD (lysergic acid diethylamide) has potential as a treatment for alcoholism, according to a retrospective analysis of studies published in the late 1960s and early 1970s.
The study, by neuroscientist Teri Krebs and clinical psychologist Pål-Ørjan Johansen of the Norwegian University of Science and Technology in Trondheim, is the first-ever quantitative meta-analysis of LSD -alcoholism clinical trials. The researchers sifted through thousands of records to collect data from randomized, double-blind trials that compared one dose of LSD to a placebo.
Of 536 participants in six trials, 59% of people receiving LSD reported lower levels of alcohol misuse, compared to 38% of people who received a placebo. “We were surprised that the effect was so clear and consistent,” says Krebs. She says that the problem with most studies done at that time was that there were too few participants, which limited statistical power. “But when you combine the data in a meta-analysis, we have more than 500 patients and there is definitely an effect,” she says. In general, the reported benefits lasted three to six months. Their findings are published today in the Journal of Psychopharmacology.
Psychedelics were promoted by psychiatrists in the 1950s as having a range of medical uses – to treat conditions such as schizophrenia, for example – before political pressures in the United States and elsewhere largely ended the work. “Alcoholism was considered one of the most promising clinical applications for LSD,” says Johansen. Alcoholics Anonymous co-founder Bill Wilson is said to have espoused the benefits of LSD in the book Pass It On: The Story of Bill Wilson and How the AA Message Reached the World.
In the last decade or so, however, a new generation of researchers have been interested in harnessing the therapeutic benefits of illicit drugs – such as 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) for post-traumatic stress disorder, ayahuasca for drug and alcohol dependency, and psilocybin, the active ingredient in hallucinogenic mushrooms, for smoking cessation.
LSD was first synthesised by the Swiss chemist Albert Hofmann in the Sandoz (now Novartis) laboratories in 1938. The laboratory had undertaken a research program aimed at isolating the active constituents of medicinal plants so that they could be produced in the laboratory and later precisely dosed for accurate administration to patients. Dr. Hofmann eventually began researching the ergot fungus and alkaloids which could be derived from it. Ergot was traditionally used by midwives as an ecbolic, a medication used to induce childbirth, and early 20th century research indicated that the various compounds in ergot had other effects on the body as well, prompting further research.
After Dr. Hofmann succeeded in synthesizing ergobasine (which became the preeminent uterotonic), he began experiments with other molecules based around the central lysergic acid component shared by ergot alkalines. Lysergic acid diethylamide, the 25th synthesized molecule (hence the name LSD-25) was developed initially as a probable analeptic, a circulatory and respiratory stimulant, based on its structural similarity to another known analeptic, Coramine (nicotinic acid diethylamide). However, no extraordinary benefits of the compound were identified during animal tests (though laboratory notes briefly mention that the animals became “restless” under its effects), and its study was discontinued.
The hallucinogenic effects of LSD were unknown for the next five years. Dr. Hofmann writes in LSD: My Problem Child that a “peculiar presentiment” prompted him to revisit LSD-25. While re-synthesizing the compound for further study, he became dizzy and was forced to stop work:
The snow globe of perception?
How psychedelics exert such effects, especially after a single dose, remains unclear. LSD and its chemical cousins share structural similarities with the neurotransmitter serotonin, which is linked to many aspects of mood, memory and pleasure. These psychedelics also bind the same receptor sites in the brain as serotonin, but there the similarity may end – studies have shown that the hallucinogens elicit chemical cascades different from other compounds that bind at the same receptor. To complicate matters further, LSD also acts at other receptors.
For the moment, studying human behavioural responses rather than brain chemistry may be more helpful in understanding how the drugs work. Robin Carhart-Harris, a psychopharmacologist at Imperial College London who has researched how psilocybin could treat depression, says that psychedelics must work at both biological and psychological levels. “Psychedelics probably work in addiction by making the brain function more chaotically for a period – a bit like shaking up a snow globe – weakening reinforced brain connections and dynamics,” he says.
Roland Griffiths, a behavioural biologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, is investigating the influence of psilocybin on smoking cessation, and says that psychedelics sometimes give rise to distinctive, insightful experiences that can produce enduring positive changes in attitude, mood and behaviour.
“This is impressive and important work,” says Matthew Johnson, a psychiatrist also at Johns Hopkins University who is now running a small trial looking at the effectiveness of psilocybin to treat nicotine addiction. “Although this meta-analysis does not replace the need to test the approach in new, well-designed and rigorous clinical trials, it puts some more muscle behind the interpretation that the older literature shows hints that psychedelic therapy might really help addiction.”
LSD Psychiatric use
LSD was introduced into the United States in 1948. Sandoz Laboratories (now Novartis) marketed LSD as a psychiatric cure-all and hailed it as a remedy for everything from schizophrenia to criminal behavior, sexual perversions and alcoholism. In psychiatry, the use of LSD by students was an accepted practice; it was viewed as a teaching tool in an attempt to enable the psychiatrist to subjectively understand schizophrenia. It was also showed great promise as a facilitating agent in psychedelic psychotherapy. In one study in the late 1950’s, Dr Humphry Osmond gave LSD to alcoholics in Alcoholics Anonymous who had failed to quit drinking. After one year, around 50% of the study group had not had a drink – a success rate that has never been duplicated by any other means.
From the late 1940s through the mid-1970s, extensive research and testing were conducted on LSD. During a 15-year period beginning in 1950, research on LSD and other hallucinogens generated over 1000 scientific papers, several dozen books, and 6 international conferences, and LSD was prescribed as treatment to over 40,000 patients. Film star Cary Grant was one of many men during the ’50s and ’60s who were given LSD in concert with psychotherapy, in an effort to overcome ‘homosexual tendencies’. Many psychiatrists began taking the drug recreationally and sharing it with friends. Dr. Leary’s experiments (see below) spread LSD usage to a much wider segment of the general populace.
The Effects of LSD
Some of the most dramatic effects of LSD reported by researchers in smaller or case studies include:
– Dramatic changes in sensations and feelings.
– Feeling several different emotions at once.
– Swing rapidly from one emotion to another.
– Altered sense of time.
– Altered sense of self.
– Crossover senses, synesthesia (hearing colors, seeing sound)
Sandoz halted LSD production in August of 1965 after growing governmental protests at its proliferation among the general populace. The National Institute of Mental Health in the United States distributed LSD on a limited basis for scientific research. Scientific study of LSD ceased circa 1980 as research funding declined, and governments became wary of permitting such research fearing that the results of the research might encourage illicit LSD use.
However, Ken Checinski, a consultant addiction psychiatrist and independent researcher based in London, says that although the results are exciting, no pharmacological treatment should be seen as a magic bullet and that modern therapeutic techniques have improved. “The included LSD trials pre-date the use of psychological techniques such as motivational interviewing and cognitive behaviour therapy,” he says.
Nature doi:10.1038/nature.2012.10200