Science

Tripping for Treatment

today2019.11.24. 26

Background

Medical use/ abuse
Jimmy Hendrix’ trademark, apart from being a gifted musician, was a bandana around his head – rumour has it, it was to hold acid (LSD) tabs to his forehead, causing the drug to slowly absorb into his skin and travel further into his blood stream – while topless hippies were dancing to his iconic guitar solos with flowers in their hair. This fictional mental picture paints the stereotypical 1960’s – Woodstock, free love and world peace – the high time of psychoactive drugs such as LSD, magic mushrooms and marijuana in the western world.
What has been an inspiration for multiple bad costume parties over the years, is not just the first but usually the only association when psychedelics are mentioned. Though hallucinogens have been used in spiritual rituals among multiple cultures for nearly 2500 years, they were largely unknown to western societies until the discovery of LSD’s mind-altering effects in 1943 (1).
 
“War on Drugs” – illegalization and stigmatization
The small but intensive peak – not unlike the short life of the great Jimmy Hendrix himself – was followed by years of misuse and in the end, illegalization. In 1971 Richard Nixon, the 37th president of the United States, declared the “war on drugs”, classifying psychoactive drugs, including LSD, MDMA (the main component of ecstasy), marijuana, psilocybin (the active substance of magic mushrooms) and heroin as Schedule 1 drugs: no medical use with a high risk for abuse. But as John Ehrlichman, Nixon’s counsel and assistant for domestic affairs, revealed in 1994, there seems to have been a different motive behind this political agenda at the time. Getting anti-war lefts (“hippies”) associated with psychedelic drugs and blacks with heroin, was Nixon’s chance to go after those two communities, when he was allegedly fighting drug abuse. This costly and counterproductive program with debatable outcomes did not only have a massive impact on society but also put the research of this field to a complete stop after just two decades – despite a promising outlook for psychiatric treatment (2).
Today, the field of psychedelic research is reemerging, although stigmatization is still jeopardizing the discussion of funding, even though many prohibited substances are approved in specific clinical scenarios, such as cocaine for nose bleeds and anaesthetic eye drops; opioids for chronic pain; and cannabinoids against the various side effects of chemotherapy. What is it so unique about psychedelics that they require stricter control? Are they really that dangerous or is it the fear of the unknown?

State of the art: the real deal
Drugs used in recent research with promising therapeutic value include MDMA, ketamine, LSD and psilocybin, all of which have psychoactive attributes but act on different systems of the brain, therefore vary in their therapeutic characteristics (3,4,5). The researches focus on treating psychiatric disorders such as post-traumatic-stress-disorder (PTSD), depression, anxiety, schizophrenia, and – ironically enough – addiction, like alcohol, nicotine or opiate use disorders. (6)
Psilocybin, found in more than a hundred types of mushrooms, is a chemical compound that works very similarly to LSD: it activates a subtype of serotonin receptors, which triggers a cascade of interesting neuronal responses (7). Regions, that usually don’t communicate, suddenly interact –causing the infamous hallucinations – an effect which hypothesized to help patients with depression to look at things from a different angle (8,9). On top of that, it decreases the activity of the default mode network, the brain’s “autopilot”, which also appears to be involved in self-reflection and autobiographical memory – explaining the effects that many users report as ego dissolution and a sense of reconnecting with themselves. This effect is also utilized in helping heavy smokers to quit their addiction (6). Therapeutically, psilocybin has a positive effect on memory and on overall well-being, and imaging-studies have also demonstrated a reduced response of the amygdala, a small part of the brain primarily associated with emotional processing of negative stimuli – the hyperactivity of which has been observed in depression (10).
Another psychoactive drug being used as a treatment of depression is ketamine, commonly known as the “horse tranquiliser” – as it has been mainly used as a veterinary anaesthetic (11). Its exceptionally fast antidepressant effect is probably due to the activation of certain glutamatergic receptors which influence numerous neurophysiological processes, such as structural reorganisation of the brain (neural plasticity), forming of new neurons (neurogenesis) and formation of new synapses – contacts between neurons (synaptogenesis) (12). Interestingly, ketamine has also shown good results in clinical trials regarding alcohol and drug addictive behaviour. There is even a proposal to use both psilocybin and ketamine to treat patients in a vegetative state or minimal conscious state, who – unlike comatose people – show signs of wakefulness, as they could trigger conscious awareness in affected patients (13).
Even MDMA, usually associated with today’s electronic music parties, has been benefiting a new approach on PTSD treatment (14). It contains classical psychotherapy accompanied by a single dose of the drug, allowing the patient to open up about traumatic experiences in a safe environment. Despite the promising early results, this treatment remains controversial as animal studies suggest that MDMA can destroy the nerve endings involved in the release of serotonin – an adverse neurological effect that has not been unequivocally proven in occasional drug users due to the lack of available data (15).
 
Advantages, risks and outlook
Though psychedelic drugs research is having a renaissance, independent and governmental funding is still very hard to come by as most psychoactive drugs are listed as Schedule 1 drugs: highly addictive and no apparent medical use (16). Research being done is facing problems like small sample sizes and there is a general lack of long-term results as well as clinical studies with a valid control group to allow linking significant results directly to the drug.
Even though the risks of abuse and addiction in particular should not be underestimated nor handled lightly, the promising potential of hallucinogenic drugs for psychiatric treatment speaks in favour for further research. Stigmatization is still an obstacle to overcome, but there is an ever growing interest in psychedelics among the population because of the increased availability on the internet, and booming tourism to experience ritualistic hallucinogenic use. The rising interest in hallucinogens is resulting in a larger number of users but the restrictions on Schedule 1 drug research also hinders research into their harmful effects. This seems to be another indication, that strict clinical use of psychedelics does not have an impact on private interest in drug taking – and important to underline, that recreational drug taking is not comparable to therapy with a healthcare professional. Instead this safe context of a controlled situation with stable conditions promises a low risk treatment with high therapeutic value – a new approach that could help people battling psychiatric problems, which are still so little understood in 2019.

 

References

  1. Carhart-Harris, RL. & Goodwin, GM. (2017) The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology42(11), 2105–2113. doi:10.1038/npp.2017.84
  2. Dyck, E. (2005). Flashback: Psychiatric Experimentation with LSD in Historical Perspective. The Canadian Journal of Psychiatry50(7), 381–388. https://doi.org/10.1177/070674370505000703
  3. Baumeister D, Barnes G, Giaroli G, & Tracy D. (2014) Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles. Ther Adv Psychopharmacol 4(4):156–169. doi:10.1177/2045125314527985
  4. Bryant, R. (2019) Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges. World Psychiatry. 18. 259-269. 10.1002/wps.20656.
  5. Singh, I, Morgan, C, Curran, H, Nutt, D, Schlag, A, & McShane, R. (2017) Ketamine treatment for depression: Opportunities for clinical innovation and ethical foresight. The Lancet Psychiatry. 4. 10.1016/S2215-0366(17)30102-5.
  6. Garcia-Romeu, A, Griffiths, R, & Johnson, WM. (2014) Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Current drug abuse reviews7(3), 157-164.
  7. Halberstadt AL. (2015) Recent advances in the neuropsychopharmacology of serotonergic hallucinogens. Behavioural brain research277, 99–120. doi:10.1016/j.bbr.2014.07.016
  8. Carhart-Harris, RL., Muthukumaraswamy, S, Roseman, L, Kaelen, M, Droog, W, Murphy, K, & Leech, R. (2016) Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences113(17), 4853-4858.
  9. Petri, G, Expert, P, Turkheimer, F, Carhart-Harris, R, Nutt, D, Hellyer, PJ, & Vaccarino, F. (2014). Homological scaffolds of brain functional networks. Journal of the Royal Society, Interface11(101), 20140873. doi:10.1098/rsif.2014.0873
  10. Kraehenmann R, Preller KH, Scheidegger M, et al. (2015). Psilocybin-induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers. Biol Psychiatry. 78:572–581.
  11. Kirby T. (2015). Ketamine for depression: the highs and lows. Lancet Psychiatry. 2(9):783-4. doi: 10.1016/S2215-0366(15)00392-2.
  12. Murrough JW. (2012). Ketamine as a novel antidepressant: from synapse to behavior. Clinical pharmacology and therapeutics91(2), 303–309. doi:10.1038/clpt.2011.244
  13. Scott, G., & Carhart-Harris, RL. (2019). Psychedelics as a treatment for disorders of consciousness. Neuroscience of consciousness2019(1), niz003. doi:10.1093/nc/niz003
  14. Feduccia AA & Mithoefer MC. (2018). MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? Prog Neuropsychopharmacol Biol Psychiatry. 84(Pt A):221-228. doi: 10.1016/j.pnpbp.2018.03.003.
  15. Gouzoulis-Mayfrank E & Daumann J. (2006). Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage? Addiction. 101(3):348-61.
  16. Nutt DJ, King LA & Nichols DE. (2013) Effects of Schedule I drug laws on neuroscience research and treatment innovation. Nat Rev Neurosci 14: 577-585. Nature reviews. Neuroscience. 10.1038/nrn3530.

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