Tools for Practice


#210 Blazing Through the Evidence on THC Versus CBD Combinations in Medical Cannabinoids.


CLINICAL QUESTION
Do tetrahydrocannabinol (THC), cannabidiol (CBD), or the THC/CBD combination yield differing benefits or harms?

BOTTOM LINE
From four randomized controlled trials (RCT), one found THC/CBD superior to THC but this was inconsistent within study and with other studies. Adverse events are prevalent in THC/CBD and individual components. While some early poor-quality research in healthy users suggest CBD may attenuate some psychiatric effects of THC, better research in real patients is needed to verify any benefits of specific components.


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EVIDENCE
Identified four RCTs comparing THC, CBD, or combined. 
  • RCT: 243 terminal cancer and weight loss patients, comparing THC/CBD versus THC versus placebo over six weeks.1 
    • THC/CBD versus THC: No statistical difference in appetite or adverse events. 
  • RCT: 177 refractory cancer pain patients on strong opioids (~270 mg morphine), comparing THC/CBD versus THC versus placebo over two weeks.2 
    • ≥30% pain reduction: 38% THC/CBD versus 21% THC, Number Needed to Treat=6. 
      • No difference for ≥10% or ≥50% pain reduction. 
    • Adverse events: No difference with THC/CBD versus THC. 
  • RCT: 48 brachial nerve injury patients, comparing THC/CBD versus THC versus placebo over two weeks.3 
    • Baseline pain 7.5/10: Both THC/CBD and THC groups reduced pain ~1.3 points, statistically significantly more than 0.6 with placebo. 
    • Adverse events not significantly different between THC/CBD and THC. 
  • ‘N of 1’ RCT: 24 chronic pain patients who benefitted from THC/CBD, compared THC/CBD versus THC versus CBD versus placebo over eight weeks.4 
    • Patients reporting equal/better pain management versus original THC/CBD.   
      • 38% THC/CBD, 33% THC, 17% CBD: Not statistically different.  
Context: 
  • RCT 120 Dravet syndrome pediatric patients: CBD reduced seizure frequency ~22% over placebo at 14 weeks.5 
    • Adverse events include somnolence (Number Needed to Harm (NNH)=4), diarrhea (NNH=5), and appetite loss (NNH=5). 
    • Recent RCT of lennox-gastaut (seizure) syndrome adults found similar.6  
  • Canadian guideline recommends cannabinoids only in refractory neuropathic pain, palliative cancer pain, chemotherapy-associated nausea/vomiting, and spasticity.7 
  • One guideline recommends low THC or high CBD:THC ratios to diminish THC adverse events.8 
    • Largely based on small studies of healthy volunteers (some with other drug use history) examining MRI or short-term scale changes.   
April 23, 2018

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Author(s):

  • Danielle Perry RN
  • G. Michael Allan MD CCFP
  • Joey Ton PharmD

1. Strasser F, Luftner D, Possinger L, et al. J Clin Oncol. 2006; 24(21):3394-400.

2. Johnson JR, Burnell-Nugent M, Lossignol D, et al. J Pain Symptom Manage. 2010; 39(2):167-79.

3. Berman J, Symonds C, Birch R. Pain. 2004; 112(3):299-306.

4. Notcutt W, Price M, Miller R, et al. Anaesthesia. 2004; 59(5):440-52.

5. Devinsky O, Cross JH, Laux L, et al. N Engl J Med. 2017; 376(21):2011-20.

6. Thiele EA, Marsh ED, French JA, et al. Lancet. 2018; 391:1085-96.

7. Allan GM, Ramji J, Perry D, et al. Can Fam Physician. 2018; 64(2):111-20.

8. Fischer B, Russell C, Sabioni P, et al. Am J Public Health. 2017 Aug; 107(8):1277.

Authors do not have any conflicts of interest to declare.