Tuesday, January 17, 2017

Hallucinogens in mental health

Hallucinogenic drugs such as LSD, psilocybin, and ayahuasca have been used to treat depression and addictions, and to help with the psychological well-being of patients suffering advanced stages of cancer.  

Terminally Ill  Patients

Jan Hoffman's article, published on December 1, 2016 in The New York Times, describes some of the research supporting the use of psilocybin for treating psychological suffering in cancer patients.* 
The most recent major study supporting this was published by Stephen Ross et al. in the December 2016 edition of The Journal of Psychopharmacology.     In this study, 29 cancer patients suffering from anxiety and depressive symptoms were given either 0.3 mg/kg of psilocybin, or an active placebo of niacin.  They received only one single dose!   There were no serious side effects.  The psilocybin doses led to large, sustained relief of anxiety and depression symptoms, following an immediate hallucinogenic, mystical effect which lasted about 6-7 hours.  Response and remission rates for depression and anxiety symptom scores were significantly larger, compared to placebo, than what we would typically see for most other established therapeutic modalities, such as conventional psychotherapy or antidepressants.  And these beneficial effects appeared to persist for up to 8 months.

In another study published in the same edition of this journal, by Griffiths et al., 51 anxious or depressed participants with life-threatening cancer received a low dose (~.01 mg/kg) and a high dose (~0.3 mg/kg)  of psilocybin,  5 weeks apart.    The authors found that the higher dose led to significant relief of anxiety and depression symptoms (final symptom scores were about 30% of the initial scores), which persisted over 6 months of follow-up.  Interestingly, reports outside of the usual depressive symptom score domain also changed in a positive way; for example, there were substantial increases in "positive attitudes about life."  A majority of subjects considered the experience with this therapy to have been very meaningful and significant.   The amount of symptom improvement was correlated with the intensity of the experience on the dosage day.   Once again, there were no severe side effect problems.  Blood pressure increases of up to 20 mm Hg could be expected.

Treatment-Resistant Depression

Here is a reference to another study published in the prestigious journal Lancet Psychiatry by Carhart-Harris et al. in July 2016: ****  This was an open-label study of 12 people with severe, treatment resistant depression.  They received a first dose of 10 mg psilocybin, followed by a second dose of 25 mg one week later.  They did not receive any further doses!    They were followed after this for 3 months.  Remarkably, there was a substantial reduction in depression severity scores which persisted at all follow-up points.  58% of the patients showed a response, and 42% of the patients showed full remission after 3 months.  


Others have used so-called "microdoses" of hallucinogens on a more regular basis,  typically about 10% of a typical recreational dose every 4 days (e.g. an LSD microdose would be about 10 micrograms).   This is too low to produce a dramatic subjective hallucinogenic effect, but anecdotally can lead to a sustained relief of depression.  Here is a reference to Alex Williams' January 7, 2017 article in The New York Times describing a case example of this practice:  **


Hallucinogens have also been used to treat addictions.  Here is a reference to a study showing very good long-term abstinence rates (67% after 1 year) in smokers treated with 2-3 doses of psilocybin (0.3 - 0.4 mg/kg) in combination with CBT:  ***

 In another small study, two doses of psilocybin were given, 4 weeks apart (0.3 mg/kg, then 0.4 mg/kg) to patients with alcohol dependence. *****   The patients were followed for 36 weeks, and had a dramatic, sustained reduction in heavy drinking days (reduction from 40% to about 10-15%).


Hallucinogens remain illegal in most places.  The quality and dose of hallucinogens available on the street might be very uncertain.

I have seen people whose experience with these agents appears to have helped them substantially.

But I have also seen people over the years who have used hallucinogens periodically, yet still suffer from a variety of psychological problems, including depression, anxiety, and addictions.

While the studies mentioned above have been very reassuring about toxicity risks and side effect problems, it would of course be very important to understand better any of the possible risks associated with this type of approach.   Patients with bipolar or psychotic symptoms might be at particular risk of harm from hallucinogens, though I would be interested to see better evidence of such risks.

If hallucinogens do have a role in treating various types of psychological suffering, I think it is likely that  they would have to be used with great care, probably in combination with a very safe, gentle, supportive milieu, and in combination with psychotherapy.  Arguably, some aspects of the benefit might be due to a "catalytic" effect when used in a safe, therapeutic setting, or as an augmentation to psychotherapy.

I would be interested to see more carefully conducted, randomized controlled studies of hallucinogens, so we could understand this issue better.  I think there is some urgency to get going with these studies, since the preliminary evidence seems so very promising.  The most likely dosing schedule for hallucinogens would be very infrequent, which would cause such treatments to be economically very inexpensive.  But as a result, we would not be seeing large-scale corporate funding for research into this!   Also, parts of the research community may have quite orthodox beliefs about non-standard treatment regimes such as this, which might cause delays in setting up good studies quickly.