Beyond cannabis: why we should look at legalising other illegal drugs for medical use to benefit patients

The UK government has finally realised the value of cannabis as a medicine, but it must not ignore the medical potential of other Schedule 1 drugs, such as psilocybin, LSD and MDMA.

one hand open one hand closed with magic mushroom

Steps being taken to legalise medical cannabis for Billy Caldwell, and others living with intractable epilepsy, are a welcome breath of fresh air. For nearly 50 years, the UK government has denied the therapeutic benefits of cannabis, and thousands of patients and their families may have suffered as a result of its antiquated legislation. But cannabis will be legalised for medical use from 1 November 2018, in response to a review by the UK’s chief medical officer, Dame Sally Davies, who confirmed that some preparations of cannabis are, indeed, medicines.

On 1 November 2018, cannabis will move from Schedule 1 (drugs that have no therapeutic value) to Schedule 2 (drugs that can be prescribed). This change of heart makes one wonder if there are other drugs in Schedule 1 that might also be eligible for rescheduling — the answer to which is a resounding ‘yes’. Several drugs currently in Schedule 1 have proven medical value, and some were once medicines: psilocybin (the active ingredient in magic mushroom), LSD and even MDMA (the original active element in the recreational drug ecstasy).

Pharmaceutical company Sandoz realised LSD’s potential in helping researchers understand the mind when Albert Hofmann accidentally discovered it in the late 1940s. The company made the drug available to certified researchers around the world, who tested it in several psychiatric disorders. Positive results encouraged more investment from national research agencies; between 1953 and 1967, the US government awarded around 140 grants on the therapeutic value of psychedelics. These studies showed significant benefits in a range of psychiatric disorders, especially alcoholism and neurotic disorders (which, today, we would call anxiety and depression)[1]
. During this time, six trials were conducted on LSD’s effect on alcoholism. In 2012, a meta-analysis of trials published between 1966 and 1970 found that just one dose of LSD had significant short-term benefits in decreasing alcohol misuse and improving abstinence[2]
.

LSD’s efficacy led Sandoz to explore the therapeutic potential of other psychedelics. Hofmann realised that the described brain effects of magic mushrooms, which had been used in many cultures for millennia, were similar to those of LSD, and he identified the active ingredient as psilocybin[3]
. Sandoz developed the drug, and, from the late 1950s, sold it as the medicine Indocybin.

In the UK, both LSD and psilocybin now sit in Schedule 1, for drugs said to have “no therapeutic value”; this lack of value is clearly untrue[4]
. By definition, Schedule 1 drugs must cause significant harm; this is also untrue of psilocybin, which, according to the Global Drug Survey 2017, is the safest recreational drug.

LSD was widely used for recreation in the 1960s, and is now associated with the counter-culture movement that started as a protest against the Vietnam War and spread to become a national movement for political change — something that the US government is thought to have seen as a threat to the status quo[5]
. Despite anti-LSD sensationalism at the time, there were little data to support that LSD was unsafe[6]
; however, the drug was banned in the United States and the UK, and later became controlled under the UN’s Convention on Psychotropic Substances 1971. These acts of prohibition were conducted with seemingly no consideration of the medical properties of these drugs and without any significant protests from the medical professions. Since the ban, the US government has not funded a single clinical study on these drugs, and the UK government has funded just one — our open-label feasibility study of psilocybin for treatment-resistant depression at Imperial College London, funded by the Medical Research Council (MRC)[7]
.

The past 50 years of denying access to these drugs have seen the worst ever censorship of scientific research, affecting the lives of millions of patients. At a conservative estimate, over the past half-century, 150 million people worldwide have died prematurely owing to alcoholism[8]
; if LSD could have helped, for example, only 10% achieve abstinence, around 15 million premature deaths could have been prevented. As with the cannabis ban, it is the patients and their relatives who suffer at the hands of politicians.

Groups in the UK and the United States are beginning to challenge this censorship and are starting to overcome this situation. It is possible to get a licence to study psilocybin for clinical research, but as psilocybin is classified as both a Class A and Schedule 1 drug in the UK, it is treated with greater stringency than much more addictive and dangerous drugs such as heroin (diamorphine, in Schedule 2). Doctors are trusted to prescribe heroin and other strong opioids, but to research psilocybin one needs a higher level security clearance check and a series of special licences which cost thousands of pounds. Similar conditions apply in the United States.

In the past decade, our group in the UK and several in the United States have published the results of clinical trials of psilocybin. In our MRC-funded open trial of a single 25mg psilocybin dose in patients with depression resistant to at least two prior antidepressant drugs, the results lent preliminary support for the safety and efficacy of this treatment[7]
. In the United States, two placebo-controlled trials in end-of-life depression or anxiety have been conducted,
both with very positive outcomes[9]
,[10]
. Two studies of psychotropic drugs for the treatment of addiction have also been conducted: one in smoking and another in alcoholism. Here, a couple of doses of psilocybin were given a few weeks apart during conventional abstinence-based treatment regimens. In the smoking trial, 12 out of 15 smokers quit completely for over 9 months[11] — a remarkable outcome, and probably the most powerful one ever in a tobacco cessation trial. And in the alcoholism study, there were highly significant reductions in drinking days and amount of alcohol drunk[12]
. In light of these successes, a multicentre clinical trial in Europe was scheduled to begin in September 2018[13]
.

In these cases, the efficacy of psilocybin was immediate. Treatment comprises one or two administrations with appropriate psychotherapy — quite different from the current psychiatric approach of taking a medicine every day. The treatments seem to work by enabling patients to find an understanding of, or even a solution to, their illness rather than keeping symptoms alone at bay with current treatments[14]
.

The illegal drug MDMA also has value as a medicine. It was widely used in couples psychotherapy when it was called ‘empathy’. Once it entered the recreational scene, its name changed to ‘ecstasy’ and it was banned. But, in the United States, the Multidisciplinary Association for Psychedelic Studies fought to restore MDMA’s place as a medicine, conducting several studies of
MDMA for the treatment of post-traumatic distress disorder that had not responded to conventional psychiatric medicines and psychotherapeutic approaches, and with considerable clinical success[15]
.

Patients regularly contact our group, and other research groups, to ask for these treatments for their intractable illnesses, and we are powerless to help. Perhaps now the chief medical officer could review the scientific literature and come to the same conclusion for these drugs, as with cannabis. These drugs are medicines and should be taken out of Schedule 1 so that pharmaceutical scientists can easily and properly research them.

David Nutt is the Edmond J Safra professor of neuropsychopharmacology at Imperial College London; chair of DrugScience.org; scientific adviser to COMPASS Pathways.

References

[1] Rucker JJH, Iliff J and Nutt DJ. Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology 2017; Epub ahead of print. pii: S0028-3908(17)30638-X. doi: 10.1016/j.neuropharm.2017.12.040

[2] Krebs TS & Johansen PO. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J Psychopharmacol 2012;26(7):994–1002. doi: 10.1177/0269881112439253

[3] Hofmann A, Heim R, Brack A et al. Psilocybin und psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen. Helvetica Chimica Acta 1959:42(5):1557–1572. doi: 10.1002/hlca.19590420518

[4] Nutt DJ, King LA & Nichols DE. Effects of Schedule I drug laws on neuroscience research and treatment innovation. Nat Rev Neurosci 2013;14(8):577–585. doi: 10.1038/nrn3530

[5] Wesson DR. Psychedelic drugs, hippie counterculture, speed and phenobarbital treatment of sedative-hypnotic dependence: a journey to the Haight Ashbury in the sixties. J Psychoactive Drugs 2011;43(2):153–164. doi: 10.1080/02791072.2011.587708

[6] Multidisciplinary Association for Psychedelic Studies. The banning of psychedelic drugs. In: Human psychedelic research: a historical and sociological analysis. 1999. Available at: https://maps.org/index.php?option=com_content&view=article&id=5468#banningpsychedelics (accessed October 2018)

[7] Carhart-Harris RL, Bolstridge M et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry 2016;3(7):619–627. doi: 10.1016/S2215-0366(16)30065-7

[8] GBD 2016 Alcohol Collaborators. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2018;392(10152):1015–1035. doi: 10.1016/S0140-6736(18)31310-2

[9] Griffiths RR, Johnson MW, Carducci MA et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol 2016;30(12):1181–1197. doi: 10.1177/0269881116675513

[10] Ross S, Bossis A, Guss J et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol 2016;30(12):1165–1180. doi: 10.1177/0269881116675512

[11] Johnson MW, Garcia-Romeu A, Cosimano MP et al. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol 2014;28(11):983–992. doi: 10.1177/0269881114548296

[12] Bogenschutz MP, Forcehimes AA, Pommy JA et al. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol 2015;29(3):289–299. doi: 10.1177/0269881114565144

[13] COMPASS Pathways. COMPASS Pathways receives FDA approval for psilocybin therapy clinical trial for treatment-resistant depression. 22 August 2018. Available at: https://compasspathways.com/compass-pathways-receives-fda-approval-for-psilocybin-therapy-clinical-trial-for-treatment-resistant-depression/ (accessed October 2018)

[14] Carhart-Harris RL & Nutt DJ. Serotonin and brain function: a tale of two receptors. J Psychopharmacol 2017:31(9):1091–1120. doi: 10.1177/0269881117725915

[15] Multidisciplinary Association for Psychedelic Studies. MDMA-assisted psychotherapy. 2018. Available at: https://maps.org/research/mdma (accessed October 2018)

Last updated
Citation
The Pharmaceutical Journal, PJ, October 2018, Vol 301, No 7918;301(7918):DOI:10.1211/PJ.2018.20205613

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