Mouse Explains Why Some Marijuana Products Not Work Well

I have found for years that pure cannabinoid (CBD) seemed to have little impact in significant = more likely neuropathic pain.  I tired to get subjects to at least have 1/4 portion of THC but elderly subjects would have nothing to do with spacing out meds. Now the animal model has shown that pure CBD has little impact on neuropathic pain. Marijuana sites pride themselves in regulating cannabis doses as they consider doctors  idiots when it comes to that. However, when you look at their titrations, it is very down-scaled and not likely to have impact for 3-6 weeks. Due to expense, many of my trial users give up on the med.

Sepulveda, Diana E., et al.
Combinations of Cannabidiol and Δ9-Tetrahydrocannabinol in Reducing Chemotherapeutic Induced Neuropathic Pain.
Biomedicines 10.10 (2022): 2548

THC needed for much relief in neuropathic pain in the mouse model

Some reviews of Marijuana have not been very complementary:

Stockings E, Campbell G, Hall WD, Nielsen S, Zagic D, Rahman R, Murnion B, Farrell M, Weier M, Degenhardt L.
Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain. 2018 Oct;159(10):1932-1954

Evidence for effectiveness of cannabinoids in CNCP (chronic non-cancer pain) is limited. “Effects suggest that number needed to treat to benefit is high, and number needed to treat to harm is low, with limited impact on other domains. It seems unlikely that cannabinoids are highly effective medicines for CNCP.”

A study that quoted them described results succinctly:
Goel A. Review: In chronic noncancer pain, cannabinoids reduce pain (NNT [ number needed to treat] 24) but increase adverse events (NNH [number needed to harm] 6). Ann Intern Med. 2018 Dec 18;169(12):JC62

Their conclusion was that you needed to treat 24 people to help one but 1/6 could get sick from it.

Another study was also uncomplimentary:

Campbell, Gabrielle, et al.
Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study.
The Lancet Public Health 3.7 (2018): e341-e350.

“Interpretation – Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain.”

Now it is becoming more clear why cannabis fails so much:

  • It is less effective in mechanical pains than neuropathic though I am suspicious of any severer pain having neuropathic features even it they lack numbness/weakness and sciatica like features.
  • THC needs to be part of the mix:
    initial study I mentioned  above found that in mice,  “We also found that high THC extract or pure THC is the most efficacious treatment for reducing neuropathic pain”

To be fair, uncontrolled trials did find benefit of cannabinoids in some pains but only in neuropathic pain:

Ueberall MA, Essner U, Mueller-Schwefe GH. Effectiveness and tolerability of THC:CBD oromucosal spray as add-on measure in patients with severe chronic pain: analysis of 12-week open-label real-world data provided by the German Pain e-Registry. J Pain Res. 2019 May 20;12:1577-1604

“improvement was significantly superior in the neuropathic pain subgroup (n=497, 62.1%) vs those with mixed (n=249, 31.1%; ASR-9: 18.2±12.0, median: 19, range: -12 to 42%) or nociceptive pain (n=54, 6.8%; ASR-9: -11.9±10.5, median: -11, range: -41% to 12%; p<0.001 for each).\

The above confirmed that it only worked in 6.8% of mechanical “nociceptive” pains but worked in 62.1% of neuropathic pains to some degree.

Comment – I am no expert on cannabis use so cannot claim to give you good advice but several things seems obvious:

  • you can try pure cannabis and it might help through promoting sleep and a bit on pain; but if pain is severe, it is not likely to give the benefits you are looking for.
  • THC ( the mind altering portion) needs to be part of the mix. I like to start with THC:CBD 1 to 4 but company often either annoyingly have no THC or 50% THC.  I would suggest getting both 0 and 50% products and mixing 1 to 1 toget the  1:4 25% THC ratio and trying that.
  • titrating doses is onerous and I am not sure my attitude of going quicker is a good idea. What needs to be considered, is that using the cannabis company’s program, it could take up to 6 weeks to engender benefit.  One has to pay the cost of a repeat prescription at one month despite not noticing any benefit at that point which I know it hard to do given the costs.
  • For severer pains, I think ketamine is a a better bet and have published a poster study here:
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