Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Effects of Schedule I drug laws on neuroscience research and treatment innovation

Abstract

Many psychoactive drugs are used recreationally, particularly by young people. This use and its perceived dangers have led to many different classes of drugs being banned under national laws and international conventions. Indeed, the possession of cannabis, 3,4-methylenedioxy-N-methylamphetamine (MDMA; also known as ecstasy) and psychedelics is stringently regulated. An important and unfortunate outcome of the controls placed on these and other psychoactive drugs is that they make research into their mechanisms of action and potential therapeutic uses — for example, in depression and post-traumatic stress disorder — difficult and in many cases almost impossible.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Nutt, D. J., King, L. A., Saulsbury, W. & Blakemore, C. Development of a rational scale for assessing the risks of drugs of potential misuse. Lancet 369, 1047–1053 (2007).

    Article  PubMed  Google Scholar 

  2. Nutt, D. J., King, L. A. & Phillips, L. D. Drug harms in the UK: a multicriteria decision analysis. Lancet 376, 1558–1565 (2010).

    Article  PubMed  Google Scholar 

  3. [No authors listed]. Prisons & drug offenders. DrugWarFacts.org [online], (2008).

  4. United Nations. Single Convention on Narcotic Drugs. UNODC [online], (1961).

  5. United Nations. Convention on Psychotropic Substances. UNODC [online], (1971).

  6. United Nations. Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. UNODC [online], (1988).

  7. Title 21 United States Code (USC) Controlled Substances Act. www.deadiversion.usdoj.gov[online]

  8. Nichols, D. E. Hallucinogens. Pharmacol. Ther. 101, 131–181 (2004).

    Article  CAS  PubMed  Google Scholar 

  9. El-Mallakh, R. S. & Abraham, H. D. MDMA (Ecstasy). Ann. Clin. Psychiatry 19, 45–52 (2007).

    Article  PubMed  Google Scholar 

  10. Danovitch, I. & Gorelick, D. A. State of the art treatments for cannabis dependence. Psychiatr. Clin. North Am. 35, 309–326 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Abrams, D. I. et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology 68, 515–521 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Zajicek, J. P. et al. Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J. Neurol. Neurosurg. Psychiatry 83, 1125–1132 (2012).

    Article  PubMed  Google Scholar 

  13. The Misuse of Drugs Act (UK). legislation.gov.uk [online], (1971).

  14. The Misuse of Drugs Regulations (UK). legislation.gov.uk [online], (2001).

  15. Grob, C. S. et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch. Gen. Psychiatry 68, 71–78 (2011).

    Article  CAS  PubMed  Google Scholar 

  16. Strassman, R. J. Human hallucinogenic drug research in the United States: a present-day case history and review of the process. J. Psychoactive Drugs 23, 29–38 (1991).

    Article  CAS  PubMed  Google Scholar 

  17. Nutt, D. J. Guerilla psychopharmacology: a new approach to research in challenging areas. Pharmacol. Matters 5, 7–9 (2012).

    Google Scholar 

  18. Pertwee, R. G. The pharmacology of cannabinoid receptors and their ligands: an overview. Int. J. Obes. 30, S13–S18 (2006).

    Article  CAS  Google Scholar 

  19. Herkenham, M. et al. Cannabinoid receptor localization in brain. Proc. Natl Acad. Sci. USA 87, 1932–1936 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Reynolds, J. R. On the therapeutic uses and toxic effects of cannabis indica. Lancet 135, 637–683 (1890).

    Article  Google Scholar 

  21. Advisory Council on the Misuse of Drugs. Cannabis: classification and public health (2008). gov.uk [online], (2008).

  22. Weissenborn, R. & Nutt, D. J. Popular intoxicants: what lessons can be learned from the last 40 years of alcohol and cannabis regulation? J. Psychopharmacol. 26, 213–220 (2012).

    Article  PubMed  Google Scholar 

  23. Passie, T., Emrich, H. M., Karst, M., Brandt, S. D. & Halpern, J. H. Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence. Drug Test. Anal. 4, 649–659 (2012).

    Article  CAS  PubMed  Google Scholar 

  24. Strohbeck-Kuehner, P., Skopp, G. & Mattern, R. Cannabis improves symptoms of ADHD. Cannabinoids 3, 1–3 (2008).

    Google Scholar 

  25. Englund, A. et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J. Psychopharmacol. 27, 19–27 (2013).

    Article  CAS  PubMed  Google Scholar 

  26. Morgan, C. J. A., Freeman, T. P., Schafer, G. L. & Curran, H. V. Cannabidiol attenuates the appetitive effects of Δ9-tetrahydrocannabinol in humans smoking their chosen cannabis. Neuropsychopharmacology 35, 1879–1885 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pertwee, R. G. et al. The psychoactive plant cannabinoid, Δ9-tetrahydrocannabinol, is antagonized by Δ8- and Δ9-tetrahydrocannabivarin in mice in vivo. Br. J. Pharmacol. 150, 586–594 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. National Institutes of Health Guide. Announcement of the department of health and human services' guidance on procedures for the provision of marijuana for medical research. NIH Guide [online], (1999).

  29. King, L. Are current attempts to control new synthetic cannabinoids futile? DrugScience (online), (2012).

    Google Scholar 

  30. Loewinger, G. C., Oleson, E. B. & Cheer, J. F. Using dopamine research to generate rational cannabinoid drug policy. Drug Test. Anal. 5, 22–26 (2013).

    Article  CAS  PubMed  Google Scholar 

  31. Stella, N. & Kline, T. Composition and methods of treating glioblastoma. World Intellectual Property Organisation Publication Number WO 2012/024670 A2 (2012).

  32. Grinspoon, L. & Bakalar, J. B. Psychedelic Drugs Reconsidered (Basic Books, 1979).

    Google Scholar 

  33. Grinspoon, L. & Bakalar, J. B. Can drugs be used to enhance the psychotherapeutic process? Am. J. Psychother. 40, 393–404 (1986).

    Article  CAS  PubMed  Google Scholar 

  34. Greer, G. R. & Tolbert, R. A method of conducting therapeutic sessions with MDMA. J. Psychoactive Drugs 30, 371–379 (1998).

    Article  CAS  PubMed  Google Scholar 

  35. Ricaurte, G. A., Yuan, J., Hatzidimitriou, G., Cord, B. J. & McCann, U. D. Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA (ecstasy). Science 297, 2260–2263 (2002); retraction Science 301, 1479 (2003).

    Article  CAS  PubMed  Google Scholar 

  36. Advisory Council on the Misuse of Drugs. MDMA (ecstasy): a review of its harms and classification under the Misuse of Drugs Act 1971. gov.uk [online], (2009).

  37. Green, A. R., O'Shea, E. & Colado, M. I. A review of the mechanisms involved in the acute MDMA (ecstasy)-induced hyperthermic response. Eur. J. Pharmacol. 500, 3–13 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. King, L. A. & Corkery, J. M. An index of fatal toxicity for drugs of misuse. Hum. Psychopharmacol. 25, 162–166 (2010).

    Article  CAS  PubMed  Google Scholar 

  39. Nutt, D. J. Equasy — an overlooked addiction with implications for the current debate on drug harms. J. Psychopharmacol. 23, 3–5 (2009).

    Article  CAS  PubMed  Google Scholar 

  40. Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L. & Doblin, R. The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J. Psychopharmacol. 25, 439–452 (2010).

    Article  PubMed  Google Scholar 

  41. Mithoefer, M. C. et al. Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. J. Psychopharmacol. 27, 28–39 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bedi, G., Luan Phan, K., Angstadt, M. & de Wit, H. Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology (Berl.) 207, 73–83 (2009).

    Article  CAS  Google Scholar 

  43. Bedi, G., Hyman, D. & de Wit, H. Is ecstasy an “empathogen”? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others. Biol. Psychiatry 68, 1134–1140 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Huot, P. et al. Characterization of 3,4-methylenedioxymethamphetamine (MDMA) enantiomers in vitro and in the MPTP-lesioned primate: R-MDMA reduces severity of dyskinesia, whereas S-MDMA extends duration of ON-time. J. Neurosci. 31, 7190–7198 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Edut, S., Rubovitch, V., Schreiber, S. & Pick, C. G. The intriguing effects of ecstasy (MDMA) on cognitive function in mice subjected to a minimal traumatic brain injury (mTBI) Psychopharmacology 214, 877–889 (2011).

    Article  CAS  PubMed  Google Scholar 

  46. Gladstone, D. J. & Black, S. E. Enhancing recovery after stroke with noradrenergic pharmacotherapy: a new frontier? Can. J. Neurol. Sci. 27, 97–105 (2000).

    Article  CAS  PubMed  Google Scholar 

  47. Nutt, D. J. Perverse effects of the precautionary principle: how banning mephedrone has unexpected implications for pharmaceutical discovery. Adv. Psychopharmacol. 1, 35–36 (2011).

    Article  Google Scholar 

  48. Bird, S. Mephedrone and cocaine: clues from Army testing. Straight Statistics [online], (2011).

    Google Scholar 

  49. Lee, M. A. & Shlain, B. Acid Dreams: The Complete Social History of LSD, the CIA, the Sixties and Beyond 93 (Grove, 1985).

    Google Scholar 

  50. Masters, R. & Houston, J. The Varieties of Psychedelic Experience: The Classic Guide to the Effects of LSD on the Human Psyche (Park Street, 1971).

  51. Krebs, T. & Johansen, P.-Ø. Lysergic acid diethylamide (LSD) for alcoholism: a meta-analysis of controlled trials. J. Psychopharmacol. 26, 994–1002 (2012).

    Article  PubMed  Google Scholar 

  52. Grof, S. LSD Psychotherapy 4th edn (Multidisciplinary Association for Psychedelic Studies, 2001).

    Google Scholar 

  53. Drugs Act 2005 (UK). legislation.gov.uk [online], (2005).

  54. Moreno, F. A., Wiegand, C. B., Taitano, E. K. & Delgado, P. L. Safety, tolerability and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J. Clin. Psychiatry 67, 1735–1740 (2006).

    Article  CAS  PubMed  Google Scholar 

  55. Sewell, R. A., Halpern, J. H. & Pope, H. G. Jr. Response of cluster headache to psilocybin and LSD. Neurology 66, 1920–1922 (2006).

    Article  PubMed  Google Scholar 

  56. Griffiths, R. R., Richards, W. A., McCann, U. & Jesse, R. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berl.) 187, 268–283 (2006).

    Article  CAS  Google Scholar 

  57. Griffiths, R., Richards, W., Johnson, M., McCann, U. & Jesse, R. Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J. Psychopharmacol. 22, 621–632 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Weber, E. T. & Andrade, R. Htr2a gene and 5-HT2A receptor expression in the cerebral cortex studied using genetically modified mice. Front. Neurosci. 4, 36 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Friston, K. J. & Kiebel, S. J. Cortical circuits for perceptual inference. Neural Netw. 22, 1093–1104 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Andrade, R. Serotonergic regulation of neuronal excitability in the prefrontal cortex. Neuropharmacology 61, 382–386 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F., Babler, A., Vogel, A. H. & Hell, D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 9, 3897 (1998).

    Article  CAS  PubMed  Google Scholar 

  62. Carhart-Harris, R. L. et al. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc. Natl Acad. Sci. USA 109, 2138–2143 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Carhart-Harris, R. L. Using MEG to characterise the mechanism of action of psilocybin in human volunteers. Br. Neurosci. Assoc. Abstr. 22, P3-D-092 (2013).

    Google Scholar 

  64. Carhart-Harris, R. L. et al. Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin. Br. J. Psychiatry 200, 238–244 (2012).

    Article  CAS  PubMed  Google Scholar 

  65. Carhart-Harris, R. L. et al. Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis. Schizophr. Bull. 8 Oct 2012 (doi:10.1093/schbul/sbs117).

  66. Robbins, T. R., Everitt, B. & Nutt, D. J. The Neurobiology of Addiction: New Vistas (OUP, 2010).

  67. Stotts, A. L., Dodrill, C. L. & Kosten, T. R. Opioid dependence treatment: options in pharmacotherapy. Expert Opin. Pharmacother. 10, 1727–1740 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. United Kingdom House of Commons Hansard Debates for November 19th 2012. www.publications.parliament.uk[online], (2012).

  69. Michelman, S. & Rorty, J. Doing Kimbrough justice: implementing policy disagreements with the federal sentencing guidelines. Suffolk U. L. Rev. 45, 4 (2012).

    Google Scholar 

  70. The Misuse of Drugs (Amendment No.2) (England, Wales and Scotland) Regulations 2010 (UK). legislation.gov.uk [online], (2010).

  71. Karst, M., Halpern, J. H., Bernateck, M. & Passie, T. The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: an open, non-randomized case series. Cephalalgia 30, 1140–1144 (2010).

    Article  PubMed  Google Scholar 

  72. Kiefer, R. T. et al. Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label phase II study. Pain Med. 9, 1173–1201 (2008).

    Google Scholar 

  73. Fibiger, C. Psychopharmacology in crisis. Schizophr. Bull. 38, 649–650 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Morgan, C. J., Curran, H. V. & the Independent Scientific Committee on Drugs. Ketamine use: a review. Addiction 107, 27–38 (2012).

    Article  PubMed  Google Scholar 

  75. Coppola, M. & Mondola, R. Methoxetamine: from drug of abuse to rapid-acting antidepressant. Med. Hypotheses 79, 504–507 (2012).

    Article  CAS  PubMed  Google Scholar 

  76. The Misuse of Drugs (Designation)(Amendment) (England, Wales and Scotland) Order 2013. (UK). legislation.gov.uk [online], (2013).

Download references

Acknowledgements

We thank V. Curran, R. Carhart-Harris and R. Doblin for helpful comments.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to David J. Nutt or David E. Nichols.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nutt, D., King, L. & Nichols, D. Effects of Schedule I drug laws on neuroscience research and treatment innovation. Nat Rev Neurosci 14, 577–585 (2013). https://doi.org/10.1038/nrn3530

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn3530

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing