Challenging experiences to psychedelic therapy and potential harms may limit these therapies widespread use and acceptance.
Adjunctive therapy to reduce anxiety without impairing memory may be useful. The receptor action is unlikely to impair psychedelic action.
Psychiatrists will be aware of Alpha 2 agonist use for reducing the noradrenergic excess from opioid withdrawal and sleep in patients managed with psychostimulents.
Alpha 2 agonists have a long history of use in the peri-operative and intensive care setting. They have been used as sedative adjuncts to reduce anaesthetic requirements, for cardiovascular stability, to reduce emergence delirium post anaesthesia, to assist and long term ventilation to name but a few. They are a core part of Anaesthesia in veterinary medicine especially when combined with ketamine. They can blunt the sympathetic response and have traditionally been used as antihypertensives.
My suggestion is to consider a carefully titrated dose of such a drug prior to the psychedelic therapy. It may allay anxiety. It may reduce sympathetic excess.
Drugs such as clonidine are quite easy to administer, dexmedetomidine though extensively used in ICU requires greater monitoring. The traditional reversal agent Yohimbine is quite a dirty drug and really used in research. Although Atipamazole is a good reversal agent it’s really only available for vetinary medicine. Clonidine‘s action is terminated
It appears these medications are used to treat various mental health conditions.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544272/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389556/
https://pubs.asahq.org/anesthesiology/article/93/5/1345/38691/Clinical-Uses-of-2-Adrenergic-Agonists
Thanks Kristopher, I’ve been using these drugs for some time and am aware it’s use in sedation and anaesthesia. The use for ptsd is interesting. My original question is not as a long term strategy, but during the period of psychedelic intoxication. Thanks for the feedback. Regards John
Hi John. I am working on a qualitative exploration of people's experiences using psychedelics to self-treat depression and anxiety. My analysis of online communities discussing this topic thus far suggests that many believe so called 'bad trips' and negative experiences can lead to positive outcomes.
Other recently published studies are finding a similar story among those who use psychedelics on their own:
Johnstad, P. G. (2021). Day trip to hell: A mixed methods study of challenging psychedelic experiences. Journal of Psychedelic Studies.
Gashi, L., Sandberg, S., & Pedersen, W. (2021). Making “bad trips” good: How users of psychedelics narratively transform challenging trips into valuable experiences. International Journal of Drug Policy, 87, 102997.
These accounts aren't in the context of psychedelic-assisted therapy and they have their own limitations in regards to their research designs, but I think they are worthy of considering in regards to your question.
Also, in the community of people who use psychedelic drugs, benzodiazepines are commonly thought to be effective 'trip killers'. People describe them as being able to reduce the intensity of a psychedelic trip quite quickly with the trade-off of a less insightful or productive trip. I understand clonidine works differently than benzodiazepines so the same may not be true for this medication.
These accounts are something to consider, although some people also describe the opposite occurring as well as in very positive/euphoric/pleasurable psychedelic experiences leading to positive mental health outcomes.
Hi David, thanks for your comments. The potential use of psychedelic in patient populations that are recreational drug naive, and may be sceptical of the need for an intense trip (good or bad), or physically challenged by the experience. I’m thinking of an older group that may be considering the therapy for suffering, anxiety, existential crisis in the terminally ill or in a palliative care setting. They may have medical morbidity eg ischaemic heart disease that is exacerbated by a profound psychedelic experience. An adjunctive therapy such clonidine may be reasonable.
I use low dose midazolam in combination with ketamine high dose infusion for patients with significant pain in the context of opioid induced hyperalgesia often with poorly managed depression. They don’t need a full blown trip to get a positive effect on mood. I have often used high dose ketamine as an induction agent to fully anaesthetised patients in a trauma setting because of its cardiovascular stability (though more often with a little midazolam and if there cardiovascular response can tolerate then clonidine) and again seen impressive changes in mood. So it begs the question does one need to be fully conscious to have a positive response from these drugs. Not that I’m suggesting patients require or should have anaesthesia for the process.
I appreciate there is a vast range of opinions out there on how the psychedelic experience and therapies should be considered. I appreciate that many people have successfully used these agents as a therapeutic tool. Unfortunately my psychiatric and emergency department colleagues will also describe a plethora of patients who’s ”bad trips” in unsupported environments have resulted in significant psychopathology.
What I’m trying to do is offer is experience from an anaesthetic position which is essentially applied cardio-respiratory physiology and pharmacology.
All the best with your research. Regards John
It's very interesting to read about your approach to this issue and the concerns you have to deal with and manage in your patients. I'm sure that the psychedelic research and practice community would be interested in how your thoughts on this develop and what you observe in practice. I certainly am.
The consideration of what kind of psychedelic is used may be important here as well. Ketamine has only recently been grouped in the category of psychedelic drugs and works, as I'm sure you are aware, quite differently than the serotonergic psychedelics in the brain and on the body. I'm wondering if your practice and approach with Ketamine will transfer to psilocybin-assisted therapy.
I vaguely remember news about some commercial groups working on synthesizing compounds that isolate the therapeutic effects of psychedelics from the psychedelic trips they are known to produce. I find the possibility of this fascinating and quite intriguing because the use of these substances outside of the Western medical system tends to focus more so on the psychedelic experience people have and how it relates to their healing. In any case, looking forward to seeing how research and practice on this topic develop.
Thanks David, yes ketamine is a different beast than lsd, psilocybin or dmt. I think our understanding of it is a little limited. Often we get fixated on one receptor mechanism such as NMDA, when the reality is more likely a multi receptor purtubation, including sigma, serotonergic , kappa opioid, dopa and noradrenaline to name but a few.
Its interesting to speculate how these drugs would be used in a medical model. Essentially the bottom line will be the cost of staffing. So if you run a clinic using LSD that’s a lot of time and staff wages consumed on patients that are requiring support or supervision. Where as parenteral or possibly inhaled DMT would have a significantly shorter period of supervision. The question is the efficacy of the antidepressant or anti anxiety or OCD or whatever effect from a short acting agent comparable to a long acting. So I think trials between drugs needs to occur. Can you get the same effect from 30 mins compared to 8 hours? Although Ketamine may not produce the effects of the other drugs, it is legal, can be administered without as much administrative hassle, reasonably easily and it’s effects wear off relatively quickly. I will be watching this area with interest. Regards John
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