Regulation

Cannabis Rescheduling: What the Clinical Evidence Says

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Clinical Evidence Requirements for Rescheduling Cannabis

The U.S. Drug Enforcement Administration (DEA) classifies all controlled substances under five schedules (I–V) in the Controlled Substances Act (CSA). Schedule I includes drugs with “no currently accepted medical use and a high potential for abuse.” Cannabis sits alongside heroin and peyote in this category — a classification that shapes policy, research restrictions, and public perception.

On the surface, it might seem simple: if science can prove cannabis has medical value, it no longer belongs in Schedule I. But the process is complex, and the type of evidence required is highly specific.

What Kind of Evidence Is Needed?

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Schedule Criteria Examples
I No accepted medical use, high abuse potential Cannabis, Heroin, LSD
II High abuse potential, accepted medical use Oxycodone, Fentanyl
III Moderate abuse potential, accepted medical use Anabolic steroids, Ketamine
IV Low abuse potential, accepted medical use Diazepam, Lorazepam
V Lowest abuse potential, accepted medical use Cough preparations with codeine

When the U.S. Food and Drug Administration (FDA) evaluates a drug, the gold standard for approval is the randomized controlled trial (RCT). These studies use random assignment to remove bias and are considered the most reliable for proving cause-and-effect between a treatment and its outcome.

While a recent analysis shows nearly 30,000 cannabis-related studies have been conducted since the 19th century, not all meet the RCT standard required for rescheduling consideration.

The Long History of Cannabis in Medicine

Cannabis sativa has been used therapeutically for over two millennia (Russo). In the United States, the medical role changed dramatically in the 20th century:

  • 1937 – The Marihuana Tax Act effectively banned cannabis, and it was removed from the U.S. Pharmacopeia’s 12th edition.
  • 1985 – Synthetic THC formulations were approved for medical use, including:
    • Dronabinol – For HIV/AIDS-related anorexia and chemotherapy-induced nausea and vomiting (CINV).
    • Nabilone – For CINV and neuropathic pain.
  • Nabiximols – An oromucosal spray with a 1:1 THC:CBD ratio, approved in the UK and Canada for multiple sclerosis (MS) pain and spasticity. In the U.S., it remains in phase 3 clinical trials.

Strongest Clinical Evidence for Cannabis Rescheduling

A 2017 review1 by the National Academies of Sciences, Engineering, and Medicine found substantial RCT evidence supporting cannabis or cannabinoids for only three conditions:

  • Chronic pain in adults
  • Chemotherapy-induced nausea and vomiting
  • Patient-reported spasticity symptoms in multiple sclerosis

Evidence for Chronic Pain

The review identified Whiting et al. (2015) as the most comprehensive systematic review2. This included 28 RCTs with 2,454 participants, most evaluating nabiximols. The authors concluded there is substantial evidence supporting cannabis in treating chronic pain in adults.

Evidence for Chemotherapy-Induced Nausea and Vomiting (CINV)

The same Whiting review examined 28 RCTs with 1,772 participants, testing therapies such as nabilone, dronabinol, THC, levonantradol, and nabiximols. The conclusion: oral cannabinoids (dronabinol and nabilone) are effective anti-emetics for CINV.

Evidence for MS Spasticity

Two systematic reviews, including Whiting et al., found nabiximols and nabilone improved MS-related spasticity symptoms. The authors concluded there is substantial evidence supporting oral cannabinoids for this use.

Conditions With Limited or Insufficient Evidence

The National Academies review also examined a range of other conditions but found limited or inconclusive RCT evidence. These included:

  • Cancer
  • Irritable bowel syndrome
  • Tourette’s syndrome
  • Amyotrophic lateral sclerosis
  • Huntington’s disease
  • Parkinson’s disease
  • Dystonia
  • Dementia
  • Glaucoma
  • Traumatic brain injury
  • Addiction
  • Anxiety
  • Depression
  • Sleep disorders
  • Post-traumatic stress disorder
  • Schizophrenia and other psychoses

Recent Cannabis Approvals and Emerging Evidence

While only three conditions met the highest evidence threshold in 2017, new approvals are shifting the conversation. In 2018, the FDA approved Epidiolex, a CBD-based drug, for severe childhood seizure disorders such as Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. This approval recognized a clear medical use for a cannabis-derived compound — potentially undermining Schedule I’s “no medical value” premise. Post-approval studies have reinforced its long-term safety and efficacy, leading to expanded clinical use.

Recent RCTs and meta-analyses since 2018 have strengthened evidence for chronic pain relief, MS spasticity management, and seizure control. Some studies also report opioid-sparing effects in chronic pain patients. These findings, combined with expanding real-world evidence from state medical programs, are increasingly factored into policy discussions.

Regulatory Shifts and Global Context

In August 2023, the U.S. Department of Health and Human Services (HHS) formally recommended that the DEA move cannabis from Schedule I to Schedule III, acknowledging accepted medical uses and reduced abuse potential compared to its current classification. As of mid-2025, the DEA has not issued a final decision, but this recommendation represents the most significant federal reconsideration in decades.

Internationally, several countries have revised cannabis laws in response to emerging evidence. Germany’s 2024 reforms expanded medical cannabis access and partially decriminalized personal use, reflecting a broader global trend toward aligning policy with contemporary science.

What’s Next?

Three well-supported conditions may already justify reconsidering cannabis’s classification. With the HHS recommendation, expanded RCT data, and growing international policy shifts, the conversation is increasingly focused on how — not if — federal policy will align with existing science.

We welcome input from readers on randomized trials that either support or challenge cannabis’s therapeutic potential.

References (APA)

1. National Academies of Sciences, Engineering, and Medicine. (2017). The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. https://doi.org/10.17226/24625
2. Whiting, P. F., Wolff, R. F., Deshpande, S., Di Nisio, M., Duffy, S., Hernandez, A. V., … & Kleijnen, J. (2015). Cannabinoids for medical use: A systematic review and meta-analysis. JAMA, 313(24), 2456–2473. https://doi.org/10.1001/jama.2015.6358

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Lydia K. (Bsc. RN) is a cannabis writer, which, considering where you’re reading this, makes perfect sense. Currently, she is a regular writer for Mace Media. In the past, she has written for MyBud, RX Leaf & Dine Magazine (Canada), CBDShopy (UK) and Cannavalate & Pharmadiol (Australia). She is best known for writing epic news articles and medical pieces. Occasionally, she deviates from news and science and creates humorous articles. And boy doesn't she love that! She equally enjoys ice cream, as should all right-thinking people.