LSD for Generalized Anxiety Disorder

LSD for Generalized Anxiety Disorder: An Encouraging New Clinical Trial....

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A study last week published in JAMA looked to evaluate the use of LSD can be efficacious in treating moderate to severe generalized anxiety disorder and the results were potentially very exciting. New treatments for the disorder are desperately needed as the illness affects approximately 10% of US adults and up to 50% of people do not adequately respond to first line treatments, which are SSRIs. Other medications like benzodiazepines are limited by abuse potential and tolerance which make them very poor choices for daily treatment.

So how did we get to LSD being tried as a potential treatment? Well the psychodelic drug was first synthesized in 1938 and since then it has had some investigations into possible uses and recently it’s use alongside of psychotherapy showed promise with treating Generalized Anxiety disorder with one trial showing that this combination was able to reduce anxiety levels for up to 1 year after treatment. LSD also seems to be relatively safe in terms of psychological risk, adverse effects and chemical dependence.

In this study participants with confirmed generalized anxiety disorder were randomized into one of five different groups. Four received different dosages of LSD or more specifically MM120 also known as lysergide d-tartrate which is a version of LSD in a specific salt form, at 25, 50, 100 and 200 micrograms of LSD base equivalent respectively and the fifth received a placebo. Patients were given the dose orally and then monitored for 12 hours for safety with a physician on hand and they were kept in a private and “aesthetically pleasing” room with standardized music and eyeshades and were free to move around, read, write or draw as they pleased. They did have monitors who were trained in keeping participants comfortable and safe and psychotherapy was not allowed with any participants.

The study suggests that doses of 100 and 200 micrograms statistically significantly reduced anxiety and depressive symptoms greater than placebo, with the lower dosages of 25 and 50 micrograms failing to do so. These improvements happened rapidly and were present at the 4 and 8 week checks and persisted until at least 12 weeks. There were significant adverse effects related to treatment in all groups, but especially in the 100 and 200 microgram doses as almost all participants experienced some with the most common being visual perception changes such as hallucinations in 95 and 100 percent in those groups, followed by nausea in 40 and 60 percent, then headache in 35 and 28 percent, and oddly enough euphoric mood in 28 and 15 percent - which if you ask me does not sound like too terrible of an adverse effect. Also strangely enough these adverse effects were also recorded significantly in the placebo group, which still reported over a 10% rate of visual perception changes, which is just nuts to think that a placebo can be strong enough to make people believe they could be hallucinating, but that is exactly why treatments need to be tested against a placebo control - because the mind is a powerful thing and it is very easy to trick ourselves into thinking that a treatment is doing something that there is no way it could be.

Now although these rates of adverse events are high, given that LSD is known for causing perception changes and nausea, it is not surprising that the patients given high enough doses will definitely experience these symptoms. The good news is almost all of these resolved within 12 hours of treatment and there were not any significant adverse effects after treatment: there were two people who did report suicidal ideation without intent to act, but they both had a history of similar ideation and they were in the 25 microgram and placebo group respectively, so that does not seem to be significant and there was also a single participant who was hospitalized for a panic attack 97 days after the dosing day, where they received the 50 microgram dose, but it was deemed unrelated to the study drug. Three participants did have severe adverse events during treatment - with two feeling intoxicated at 50 and 100 microgram doses and one feeling significantly depressed in the 50 microgram dose, but none were reported in the 200 microgram dose or 25 microgram dose.

So what does this mean for the future? Well it seems like the study is pointing to a 100 microgram dose of the LSD salt being rapidly efficacious as a long lasting treatment for generalized anxiety disorder and depression with smaller doses lacking clearly significant improvement and higher dosages not clearly showing further improvement relative to side effects and risks. Risks and side effects seem to be mostly related to adverse events during dosing, but were well tolerated and self limited. And of course like all studies, it will require further validation and due to the obvious effects of LSD in participants, the majority of participants were able to determine if they were in fact in the treatment group or not, so it is likely impossible to produce a study that can be properly blinded from the side of the participants.

We will see how this affects the future treatment of anxiety disorders and possibly even depressive disorders, but it will take time and further study before there is any chance it will become standard practice in the future.

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