Psychedelics and psychosis: the elephant in the room

There's a lot we don't yet know about psychedelics and psychosis - like whether psychedelics can cause psychotic disorders, or possibly help treat them. But some new studies are now appearing.

It struck me the other day that Aldous Huxley, who co-invented the word ‘psychedelic’, would be excluded from the psychedelic renaissance as he had a history of psychosis in the family (his brother Julian Huxley was diagnosed with manic depression).  When did a family history of psychosis become an excluding criterion for psychedelic therapy?

In the 1950s and 1960s, psychiatrists experimented with psychedelics as a treatment for schizophrenia and manic depression. As Rucker et al report here, the results were mixed – some patients improved enough to recover and discontinue treatment, but others’ psychotic symptoms worsened. Most psychiatrists concluded psychedelics were not a good treatment for psychotic disorders.

There were still some radical outliers, like RD Laing, who ran Kingsley Hall, an experimental commune for the mentally unwell in north London, where those prone to psychosis and the doctors lived on an equal footing, and everyone took large doses of LSD. At least two people jumped off the roof, apparently.

Here is Francis Gillett, who was diagnosed with paranoid schizophrenia, and who stayed in Kingsley Hall in the 1960s:

Ronnie [Laing] said, "Go mad, young man", and I did. I took him at his word, and I went as mad as I possibly could, and at no time did he try and stop me. Yeah, [once] I leapt off the roof. I didn't go the full drop. I leapt into a junkyard, which was full of old washing machines and Hoovers and things people had thrown over the wall. I got a crash fracture in my spine that still causes me problems today.

Ronnie used to keep acid in his fridge. It was pure stuff, Sandoz laboratory grade, the real McCoy, and he wasn't shy about sharing it around. He believed it was a kind of spiritual laxative, which I think is probably quite an accurate description of it. And I do remember him handing it to me: I thought, 'This is the apple from the tree of knowledge, and if I take this it's going to be a long road back from where I'm going', but I did take it. Ronnie did believe you would be able to flush demons away with it. I wouldn't disagree, I think it's an interesting thing.

[Then there was] the DMT – Dimethyltryptamine or 'triptamine. It's refined from a plant in the Amazon jungle and we had it shipped in from California in a briefcase. I took it once, and it changed my life for ever. Just once really blew my mind, and I never really thought the same about anything again. I had a vision of myself as a dead Jew being bulldozed into a mass burial pit at Auschwitz. It was an intensely strong experience. It was the end of life, the end of existence. I felt very dead at that point.

Those were different times!

In the 1980s, DMT researcher Rick Strassman may have been the first to suggest that both psychotics and those with a family history of psychosis should not take psychedelics. And that idea was embraced by the Johns Hopkins pioneering studies in the first decade of the Noughties, which excluded any people with a family history of psychosis.

 It has become standard dogma of the psychedelic renaissance, that people with psychosis or with a ‘family history of psychosis’ should not take the drugs. In general, the industry is very keen to rehabilitate the image of psychedelics after the 1960s, especially by rejecting any link between psychedelics and psychotic experience.

Can GWAS studies predict those who have bad reactions to psychedelics? Not yet, perhaps one day.

We at the CPE project are all for psychedelic safety and harm reduction. And it may be that some cluster of genetic factors makes it more likely you will have a difficult / bad trip, or that a bad trip will lead to extended life difficulties.

In my own case, when I was a teenager I had a bad trip which led to several years of social anxiety and PTSD – I was in the unlucky minority who experienced extended life difficulties following a bad trip. I was not aware that I had any family history or genetic disposition to mental illness, so my mental health problems came out of the blue. Since then, however, a cousin experienced psychotic episodes following drug use, and a close family member was diagnosed with bipolar disorder. Which makes me wonder – were there genetic factors making me more prone to a bad psycehdelic reaction? Might it one day be possible to spot genetic markers in people and help them decide whether they want to take the risk with psychedelics?

It's strange there is no study of genetic risk factors for psychedelics, considering the field already assumes genetics do put you at greater risk. At the moment, this is an untested assumption. How might one go about testing it?

In cannabis research, studies are beginning to appear which look at possible connections between genes and psychotic experiences in cannabis smokers. This is, of course, a controversial and much-debated area. It has been speculated since the 1960s that cannabis could trigger schizophrenia – one study in 1987 found that 6% of cannabis users developed schizophrenia.

However, as this paper suggests, it could be that people who develop schizophrenic or psychotic symptoms are more likely to use cannabis to alleviate symptoms. Or it could be that people who develop psychotic disorders are more prone to risky behaviours, like drug-taking. Or that cannabis has a stronger effect on those prone to psychosis – and therefore is more likely to make them spin out. In other words, this is a very complicated area and one has to be careful before making sweeping statement

Nonetheless, some studies do suggest genetic factors make some cannabis users more likely to develop ‘cannabis use disorder’, or to experience psychotic episodes. For example, Wainberg et al (2021) used data from the UK Biobank to see if a Genome Wide Association Study (GWAS) could spot any genetic correlates between cannabis use and psychotic experiences. Wainberg’s study looked at over 100,000 people. I asked him if he found any genetic correlation, and he told me:

It varies depending on which type of psychotic experience. For some it’s quite strong, especially delusions of reference – ‘did you ever believe that a strange force was trying to communicate with you in ways that only you can detect?’ People in the top 20% genetic risk for schizophrenia were 68% more likely to report those delusions of reference if they had ever used marijuana.

I asked Wainberg if one could conceivably do a similar study looking at genetic markers in people who have bad trips or extended life difficulties after psychedelic use. He said it’s possible in theory, but much easier and a whole lot cheaper if you have a very large data set like the UK Biobank. Perhaps, eventually, one of these large genetic data banks will include questions on psychedelics in their surveys, and some studies can be run. But we’re a long way from there yet, and should be wary of some of the companies offering polygenic testing services to ‘predict’ who will have bad trips and should steer clear of psychedelics.

Can psychedelics help people prone to psychotic episodes?

Is it possible that, as well as exacerbating psychotic symptoms, psychedelics could help alleviate them?  It’s certainly the case that some people diagnosed with, say, bipolar disorder do use psychedelics to medicate themselves, and report that they find it helpful. One such was the actress Carrie Fisher, as she told the Netflix doc Have A Good Trip she felt LSD helped her feel normal and muted her symptoms from bipolar disorder.

Some others who have psychotic episodes or have received diagnoses of bipolar disorder or schizophrenia report that they use psychedelic plants to alleviate their symptoms or as an alternative to anti-psychotics. This is discussed in this online seminar from the ‘Crazywise’ movement:

However, others in the MAD / Crazywise / psychosis-survival networks say that their psychotic symptoms were triggered by psychedelic use, and won’t use psychedelics again.

This is a very under-researched area and few psychedelic researchers will go near it. It’s hard enough to get funding and approval to study psychedelics and depression or anxiety, let alone psychosis. But that’s beginning to change.

One new study by Morton et al, published in December in the Journal of Psychopharmacology, did an online survey of 541 people with a diagnosis of bipolar disorder who use psilocybin (magic mushrooms). It found that, on a five-point scale from “Not at all” to “Extremely harmful,” participants rated the harmfulness of their psilocybin experience as 1.6 on average. And they rated the perceived helpfulness of their psilocybin experience as 4 on average. However, 32.2% of participants reported experiencing negative or unwanted outcomes during or in the 14 days after a psilocybin trip - especially manic episodes. Eighteen people required emergency support during or in the 14 days after a psilocybin trip.

So that suggests that adverse psychedelic experiences are more likely for people with a diagnosis of bipolar disorder.

Meanwhile a new and as-yet unpublished paper on psychedelics as a treatment for psychosis, from LeTorre at al at the University of Ottawa interviewed 12 experts in the field of psychedelic research (anonymously). The experts suggested:

that while the exclusion criteria may be justified for psychedelic protocols that provide insufficient psychological support for participants, there was agreement that psychedelic-assisted psychotherapy is not necessarily contraindicated for all individuals with psychotic symptoms. Results suggest that highly supportive psychedelic-assisted psychotherapy may be of benefit to individuals experiencing symptoms of psychosis.

In other words, psychedelics could perhaps be a treatment for psychotic disorders, but there would need to be strong support integration protocols in place for the days and weeks after a trip. And that doesn’t exist yet.

Meanwhile, ketamine is already widely available for people diagnosed with bipolar disorder. Several clinics in the UK and US already offer it. Because ketamine has already got FDA approval as an anaesthetic, medical clinics can offer it as a treatment to anyone who requests it. You can even order it online and get it delivered to your door.

Is it safe and effective? There are some early studies and reports of its safety and effectiveness for bipolar disorder, but we’re talking small studies. There are some reports that ketamine therapy can trigger manic episodes, but also some anecdotal reports that it can help alleviate the depression symptoms of bipolar, albeit temporarily. Have a read of this reddit discussion, for example. And this heartening report of recovery. But even those who say they’ve been helped by ketamine, like the poster above, warn that it can trigger short-term mania, so there needs to be strong support in place. And it seems like you may be rolling the dice.

All in all, it’s a mixed picture. There’s a lot we don’t yet know about the relationship between psychedelics and psychosis, and a lot we need to learn.

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