This research briefing is co-published with the excellent Report on Psychedelics.

August 27th, 2021

In The Research Briefing:

• The considerable risks of ibogaine
• Psychiatrists favourable about psychedelics as medicines
• Quitting tobacco addiction after psychedelic use

IBOGAINE

Adverse events of ibogaine treatment

Psychedelics don’t come without risks. Most are physiologically safe, with for instance virtually no risks of overdosing, for instance with magic mushrooms (psilocybin) unless one stomachs 20kg in one sitting. But, not every psychedelic is made equally and there are known differences within this class of compounds. Ibogaine is one notable exception with known cardiovascular risks. Reports of seizures, gastrointestinal issues, loss of balance (ataxia), and heart failure are not uncommon.

Before we dive into the most recent review of adverse events with ibogaine, let’s first ask why it is being used in the first place. Ibogaine is known to disrupt the opioid system and thus can reduce, and temporarily eliminate, withdrawal symptoms and drug cravings. Many clinics around the world are currently treating those with substance use disorders, such as addictions to cocaine or opioids (e.g. heroin). Although promising, there hasn’t been much study on the considerable risks of ibogaine ingestion. This study lays out what we know.

The top risks of ibogaine

• Acute effects (<24 hours): QTc prolongation, where the time between contraction and relaxation of the heart chambers (cardiac ventricals)
• Prolonged adverse events (>24 hours): psychiatric alterations, with insomnia for up to two weeks, delusions, agressiveness, and hallucinations being some of the most often mentioned events
• Interactions with other drugs: where one case of ‘standard practice’ medications led to a fatal interaction

Although the risks of ibogaine alone can be characterized as graver than other psychedelics, it should be known that many (if not most) of the participants in the studies had pre-existing medical conditions and most a dependence on a variety of drugs (sometimes still present in their bodies during treatment). Or in other words, the participants don’t reflect the average population and although they may be most helped by ibogaine treatment, they are also the ones with heightened health risks.

One factor that makes assessing the risk of ibogaine treatment difficult is the variability of the amount of ibogaine and the exact substance administered (sometimes noribogaine, the active metabolite of ibogaine, was used directly). An earlier study found that the amount of ibogaine in root bark (of the Tabernanthe iboga bush) ranged from 0.6% to 11.2% (a 19-fold difference). The study analyzed both case reports from private clinics and clinical trials in hospitals. The former reported the most severe adverse events, whilst the latter only reported mild to moderate adverse events.

Although promising, ibogaine treatment doesn’t come without significant risks. For some, the risks are worth it to potentially break free from addiction. Future clinical trials should be able to better differentiate the risk at which dose level. Or second generation psychedelics such as 18-MC and Tabernanthalog could provide anti-addictive properties with lower to no cardiovascular risks. We will find out in the coming years.

PSYCHIATRY

Psychiatrists’ support for psychedelics

Psychedelic-assisted therapy will need to be administrated not by dedicated researchers but by psychiatrists and other mental health care workers. A looming question for psychedelics as medicines can be paraphrased as “are medical professionals ready to administer psychedelics in the treatment of patients?” The promising clinical trials should be able to sway many, yet a stigma is still attached to psychedelics. The current paper adds more data to answer this question by surveying 104 psychiatrists over the course of two presentations about psychedelics at psychiatry conferences.

The survey asked psychiatrists first about their knowledge of psychedelics (e.g. if they knew which psychedelics were of natural origin & which clinical trials phase psilocybin studies are). They were then asked about their attitudes towards psychedelics, the questions also asked about what ways the psychiatrists would like to be informed or educate themselves on this topic.

This is the support they found

• 80% agreed that psychedelics show promise in treating psychiatric disorders, this was 60% for treating substance use disorders (e.g. alcoholism)
• 66% indicated concerns about a lack of trained psychedelic-assisted therapists, which matches nicely with them receiving less than two hours of psychedelic training
• 70% said that patients asked about psychedelic therapy a few times (60%) or often (10%)

This level of support is quite a bit higher than one would have expected only a few years ago. The study also found that nearly half of the participants knew that MDMA trials are in phase III. Even more surprising is that a third of attendees had read ‘How to Change Your Mind‘. But, what should keep into consideration is that the participants did self-select to attend a session about psychedelics, leading to a selection bias and possibly higher support than within the general population of psychiatrists.

One final observation was that some psychiatrists were concerned about the addictive potential of psychedelics. Those were also less likely to support them for substance use disorder treatments or legalization. The current evidence and a long history of recreational use find that the risk of addiction to psychedelics is (very) low. More education about the addictive potential, teaching the differentiation between psychedelics and a misguided conception of ‘drugs’ should play a part in the training psychiatrists receive.

SMOKING

Use of psychedelics associated with stopping smoking

This week, Mydecine, a psychedelic for-profit company, announced that they have signed a five-year contract with Johns Hopkins University to study smoking cessation. The aim of the study is to find out if psychedelics can help prevent part of the 8 million deaths and billions lost in the treatment of smoking-related diseases.

The announcement comes as a pleasant surprise as smoking cessation was the topic of one of the most widely cited studies of this century. The pilot study was published in 2014 but besides a few follow-up studies didn’t attract new funding for clinical trials. This could be a large oversight with regards to psychedelics as medicines, missing one of the biggest dangers to public health for which the early study showed very promising results.

What we know at this time

• The pilot study with 15 participants showed that psilocybin-assisted therapy resulted in 80% of participants being smoking abstinent six months later (a result much better than almost any other study has shown)
• A whole five years later, 60% of participants were still not smoking. The follow-up study provided more evidence for long-term effects without any further therapy or intervention from the original study team
• A survey study of those who reported stopping smoking after a psychedelic experience found that approximately 40% had stopped smoking successfully, 30% had greatly reduced their smoking habit, and 30% had returned to smoking.

The survey study found that participants reported less severe withdrawal symptoms compared to previous quitting attempts. They also reported endorsing new values and life priorities as the reason for quitting smoking.

Although the amount of data is still very limited, the evidence is pointing towards the possibility of psilocybin/psychedelics as being a possible treatment for smoking addiction. Just like with opioid addictions with ibogaine, psilocybin seems to be able to disrupt addictive patterns. Kicking smoking may become a little bit easier in the future.

Research Report Readout

A questionnaire found that participants, right after an ayahuasca ceremony, scored significantly higher on measures of self-compassion, self-criticism, and self-reassurance. Although the study was not blinded (everyone received ayahuasca), and was taking within 24 hours after treatment, it provides promising results.

There are some known, but limited, risks of activating mania with psilocybin for those with bipolar depression (BD). A review of the literature describes 15 cases of BD and the use of a range of psychedelics.

A survey study found that psychological flexibility mediated the relationship between acute psychedelic effects (acute insight & challenging experiences) and decreases in racial trauma among BIPOC.