The British Journal of Psychiatry (2006) 188: 88-89. doi: 10.1192/bjp.188.1.88
© 2006 The Royal College of Psychiatrists
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Correspondence

Psychedelics in psychiatry

D. Arnone

Department of Mental Health - Addictive Behaviour, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.

F. Schifano

Department of Mental Health - Addictive Behaviour, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.

Correspondence: E-mail: darnone{at}sgul.ac.uk

In his editorial ‘Can psychedelics have a role in psychiatry once again?’ (Sessa, 2005), Dr Sessa offers a detailed historical and heuristic perspective of psychedelics, with particular reference to psychotherapy. Reading the article the feeling was of sensed (by the author) repulsion of the ‘neurobiological’ psychiatrist in relation to ‘research that explores alternative states of consciousness’, ‘psychedelics research’ as a ‘vi-able neurobiologial substrate for the very human experience of religious encounter’ and generally a possible use of psychedelics in psychiatry. Perhaps we are some of those psychiatrists who ‘have been conditioned to consider such work as mysticism’ but we found such a proposition challenging. We would like to discuss recent neurobiological findings related to one of the psychedelics mentioned by Dr Sessa, which perhaps would offer an explanation as to why these substances have limited scope in psychiatry today.

3,4-Methylenedioxymethamphetamine (MDMA), also known as ecstasy, is largely consumed by young adults as a recreational drug. Common doses of this popular compound (60-120 mg, equivalent to 1-2 tablets) produce unexpectedly high blood levels, with MDMA present at high concentration at the receptor level. The drug induces dose-dependent neurotoxicity in animal models and humans; this mainly involves the central serotonergic system (Ricaurte et al, 2002). Serotonin is important for brain development and maintenance of neural and glial function in the mature brain (Azmitia, 2001). Another interesting mechanism involves the ‘pruning’ of serotoninergic neurons (Ricaurte et al, 2000). The drug appears to reduce the number of serotonin axons and axon terminals but nerve cells will often replace terminals upstream for the damaged ones. The resulting effect is of substantial impaired connectivity. Younger brains are particularly susceptible because of increased neuroplasticity, resulting in a substantial reorganisation of brain connectivity.

Functional magnetic resonance imaging studies suggest a decreased activation in inferior temporal regions, the hippocampus, angular gyrus and striate cortex associated with working memory performance (Daumann et al, 2003, 2005), with the hippocampus and globus pallidus being possibly more sensitive (Reneman et al, 2001; Jacobsen et al, 2004; Daumann et al, 2005). More recent voxel-based morphometry studies support the hypothesis that the use of MDMA leads to reduction in cortical grey matter in multiple brain regions, including the neocortex, brain-stem, cerebellum and anterior cingulate gyrus, reflecting compromised serotonergic activity (Cowan et al, 2003). Although we have mentioned only a few studies, there is substantial evidence to suggest considerable neurotoxicity of compounds such as those mentioned by Dr Sessa. There are concerns about possible long-term adverse effects of psychedelics in both infrequent and regular users, which explain why psychiatrists are reluctant to consider such substances in their pharmacological armamentarium.

EDITED BY KIRIAKOS XENITIDIS and COLIN CAMPBELL

REFERENCES

  1. Azmitia, E. C. (2001) Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Research Bulletin, 56, 413 -424.[CrossRef][Medline]
  2. Cowan, R. L., Lyoo, I. K., Sung, S. M., et al (2003) Reduced cortical gray matter density in human MDMA (Ecstasy) users: a voxel-based morphometry study. Drug and Alcohol Dependence, 72, 225 -235.[CrossRef][Medline]
  3. Daumann, J., Schnitker, R., Weidermann, J., et al (2003) Neural correlates of working memory in pure and polyvalent ecstasy (MDMA) users. Neuroreport, 14, 1983 -1987.[CrossRef][Medline]
  4. Daumann, J., Fischermann, T., Heekeren, K., et al (2005) Memory-related hippocampal dysfunction in poly-drug ecstasy (3,4-methylenedioxymethamphetamine) users. Psychopharmacology, 180, 607 -611.[CrossRef][Medline]
  5. Jacobsen, J. K., Mencl, W. E., Pugh, K. R., et al (2004) Preliminary evidence of hippocampal dysfunction in adolescent MDMA (‘ecstasy’) users: possible relationship to neurotoxic effects. Psychopharmacology, 173, 383 -390.[CrossRef][Medline]
  6. Reneman, L., Majoie, C. B., Habraken, J. B., et al (2001) Effects of ecstasy (MDMA) on the brain in abstinent users: initial observations with diffusion and perfusion MR imaging. Radiology, 220, 611 -617.[Abstract/Free Full Text]
  7. Ricaurte, G. A., Yuan, J., McCann, U. D. (2000) (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-induced serotonin neurotoxicity: studies in animals. Neuropsychobiology, 42, 5 -10.[CrossRef][Medline]
  8. Ricaurte, G. A., Yuan, J., Hatzidimitriou, G., et al (2002) Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA (‘ecstasy’). Science, 297, 2260 -2263.[Abstract/Free Full Text]
  9. Sessa, B. (2005) Can psychedelics have a role in psychiatry once again? British Journal of Psychiatry, 186, 457 -458.[Free Full Text]
 

Author's reply:

B. Sessa

The Park Hospital, Old Road, Headington, Oxford OX3 7LQ, UK.

Correspondence: E-mail: drbensessa{at}hotmail.com

EDITED BY KIRIAKOS XENITIDIS and COLIN CAMPBELL

I thank Drs Arnone and Schifano for their letter, which opens the debate about the undeniable dangers of recreational drug misuse, compared with the relatively safe clinical use of MDMA. This topic has received considerable media interest, with particular attention centred on the damaged brains of users of ecstasy - an illegal compound, which may or may not contain varying amounts of MDMA, together with any other substance. Ecstasy is usually taken in combination with other illegal drugs (Curran, 1998) or large amounts of alcohol, and often in circumstances involving high temperatures, which are known to exacerbate neurotoxicity (Malberg & Seiden, 1998).

All studies referred to by Drs Arnone and Schifano involve either recreational ecstasy users (mostly with no controls for other illegal drugs) or animal models with high and frequent dosage regimes that do not relate to those used for medically supervised MDMA psychotherapy research. The approach is therefore analogous to opposing the controlled, clinical research of opiate drugs after quoting studies of the morbidity of illegal heroin users.

Physiological studies involving infrequent and moderate doses of pure MDMA (as used in the psychotherapeutic setting) consistently demonstrate that the drug causes insignificant neurotoxicity, neuropsychological, mood or memory effects (Ludewig et al, 2003; Halpern et al, 2004).

Of course, there are risks when using any treatment - even in a controlled setting. All drugs, from paracetamol to cancer chemotherapy, are potentially harmful and must only be used after considering the risks and benefits - which includes considering the risk of doing nothing.

In relation to the opening comments, as a working psychiatrist, far from being ‘repulsed’ by neurobiological psychiatry, I am acutely aware of the importance of a holistic approach. Indeed, psychedelic psychotherapy, and the complexity of issues it raises, is a startling example of the effective interplay of concurrent psychological and organic treatments.

Given their history, MDMA and the other psychedelics are contentious treatments. However, it is possible for psychiatrists to think creatively and also consider safety and realistic risk-benefit ratios.

After all, if these compounds do have the potential to improve the speed and depth of psychotherapy, then they at least deserve clinical research in order to establish whether they can be useful tools to fight the global burden of neurotic illness.

REFERENCES

  1. Curran, H.V. (1998) ‘Ecstasy’: a Human Neurotoxin? A Novartis Foundation Meeting. http://www.ecstasy.org/info/novartis1.html
  2. Halpern, J. H., Pope, H. G. Jr, Sherwood, A. R., et al (2004) Residual neuropsychological effects of illicit 3,4-methylenedioxymethamphetamine (MDMA) in individuals with minimal exposure to other drugs. Drug and Alcohol Dependence, 75, 149 -152.[Medline]
  3. Ludewig, S., Ludewig, K., Hasler, F., et al (2003) No lasting effects of moderate doses of MDMA (Ecstasy) on memory performance and mood states in healthy humans. Biological Psychiatry, 53 (suppl.), 2055 .
  4. Malberg, J. E. & Seiden, L. S. (1998) Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat. Journal of Neuroscience, 18, 5086 -5094.[Abstract/Free Full Text]



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