Is marijuana helpful for neuropathic pain?

February 8, 2023

Marijuana is the most commonly used illicit substance in the US: approx. 12% of people 12 and over have used in the past year. Approx 1 out of 3 individuals with pain have tried cannabis to treat it (ABC News 2005).

Cannabadiol Receptors

CB1: CNS and PNS
CB2: Lymphoid and immune tissues (helps mediate inflammatory response associated with pain; Mackie, 2006)

Endogenous cannabinoids: anandamide, 2-arachiodynlgycerol.

FDA Approved cannabinoids

Dronabinol (Marinol): synthetic THC in 2.5, 5 and 10 mg capsules. Syndros is the liquid form. FDA approved for chemo nausea, and appetite in HIV. Use is limited by its variable onset of action, intoxication and dysphoria. Marinol is Schedule III, Syndros is Schedule II.
Nabilone (Cesamet): synthetic THC in 1 or 2 mg doses. Schedule II.
Epidiolex: CBD. FDA approved 6/2018 for Lennox-Gastaut and Dravet

Outside of US:

Nabiximol (Sativex) 2.7 mg THC, 2.5 mg CBD (approved in Canada since 2005 for central neuropathic pain, MS, and cancer pain)
Cannador THC:CBD = 2:1

Aside: “Hemp” and marijuana are both derived from the cannabis sativa plant, but are different strains. Hemp is required to have less than 0.2% THC. A common variety of hemp strains are: Charlotte’s Web, Berry Blossom

Synthetic MJ /Spice/K2 – full agonists of CB1 and CB2 (THC is a partial agonist) associated with seizures, hallucinations, etc…

Hypothesized mechanisms to explain marijuana controlling pain (Russo)

CB receptor directly mediates analgesia.
Low anandamide levels found in migraineurs (Sarchielli, 2006)
Blocking endocannabinoids (with rimonabant) can produce hyperalgesia in mice
THC decreases 5-HT release from platelets
THC reduces NMDA responses (affecting central sensitization syndromes)
THC is a neuroprotective antioxidant (inhibits glutamate neurotoxicity), and has anti-inflammatory properties (inhibits PGE-2 synthesis, decreases platelet aggregation).
Cannabinoids reduce hyperalgesia via inhibition of calcitonin gene-related peptide.
THC stimulates beta-endorphin production
CBD inhibits TNF-alpha
Other phytocannabinoids such as CBC shows anti-inflammatory properties, and CBG exhibits GABA reuptake inhibition
Terpenoids, such as myrcene, have activity that can be blocked by naloxone, and also block inflammation via PGE-2
Flavenoids also inhibit TNF-alpha, and PGE-2

Young woman smoking vape or e-cigarette in neon blue light

Cochrane Review (2018) Cannabis‐based medicines for chronic neuropathic pain in adults

These authors searched for studies on marijuana and pain and found roughly 1400 studies, and then excluded studies where individuals had a history of substance use disorder, pain duration less than 2 weeks, fewer than 10 participants in treatment arm
In total there were 16 studies and 1750 participants. There was no “high quality” study. Difficult to blind participants with a psychoactive medication.
The 16 studies were comprised of multiple sclerosis pain (5 studies), diabetic polyneuropathy (3), plexus injury (1), spinal cord injury (1), HIV neuropathy (1), chemo neuropathy (1), peripheral of various etiologies (3), mixed central and peripheral (1).
Overall, the quality of the data was low. There was some evidence that showed marijuana provided a 30% reduction in pain however, there was a significant difference in the dropout rates due to side effects with the marijuana group compared to placebo.

Main side effects of marijuana limiting its use

Dry mouth, orthostatic hypotension, tachycardia, sedation, confusion, psychosis. Memory impairment can abate after a few weeks of abstinence.
Smoking it can lead to bronchial irritation
Cannabis hyperemesis syndrome (diagnostically similar to cyclic vomiting syndrome, as those with CVS can use MJ to self-medicate. Unlike CHS, those with CVS more likely to have a personal or family hx of migraine, psych comorbidities, have “triggers” and do not have compulsive bathing for relief)
Debate about the relationship with schizophrenia
Debate over whether there is a withdrawal syndrome

Possible treatments for marijuana dependence

Weak evidence to tx withdrawal or to modify subjective effects of marijuana

Nefazodone (450/day), naltrexone (12.5-100/day), zolpidem (12.5/day), tiagabine (6-12/day), mirtazapine (30/day), quetiapine (up to 200 mg/day)

For treatment of THC dependence

Oral THC, did not change self-administration but decreased positive effect of smoked THC (Hart, 2002)
Rimonabant (cannabinoid antagonist) decreased subjective effects of marijuana

Nabiximols (THC+CBD) as an agonist replacement for cannabis withdrawal

Study of 51 individuals randomized to 6 day regimen of nabiximol or placebo. Was found to have a significantly reduced severity of cannabis withdrawal compared to placebo, measured by irritability, depression, and cannabis cravings.

What Cerebellum Activities Are Good For ADHD?

The cerebellum is the part of the brain responsible for balance, rhythm, and coordination. Research suggests that stimulating this area can improve focus and cognitive control in individuals with ADHD. Effective activities include:

Balance Exercises: Walking on a balance beam, standing on one leg (yoga tree pose), or using a wobble board.
Coordination Drills: Juggling, skipping rope, or playing catch with a ball.
Rhythmic Movement: Dancing, martial arts (like Tai Chi or Karate), or playing a musical instrument (especially drums or piano which require limb independence).
Target Sports: Activities that require hand-eye coordination like table tennis, badminton, or tennis.

What Is The 20 Minute Rule For ADHD?

The “20-Minute Rule” is a productivity strategy designed to combat procrastination and “time blindness.” It generally refers to two similar concepts:

The “Just Do 20 Minutes” Approach: If a task feels overwhelming, commit to doing it for only 20 minutes. This lowers the barrier to entry. Often, once started, the hyperfocus kicks in, and you continue past the timer. If not, you still made progress.
The Task Switch (Pomodoro Variation): Work for 20 minutes, then take a short active break. For ADHD brains, shorter intervals (like 15–20 minutes) can sometimes be more effective than the standard 25–30 minute Pomodoro technique because the reward (break) comes sooner.

What Is The Best Exercise For ADHD Brain?

While any movement is better than none, complex aerobic exercise is often cited as the “best” for ADHD.

Aerobic Intensity: Activities that get the heart rate up (running, swimming, cycling) increase the production of dopamine, norepinephrine, and serotonin—neurotransmitters often in lower supply in ADHD brains. This mimics the effects of some ADHD medications.
Complexity: Exercises that require thinking while moving (complex motor skills) are superior. For example, Martial Arts, Rock Climbing, or Gymnastics require you to focus on the next step, balance, and strategy simultaneously. This challenges the brain’s executive functions while providing the physical release of cardio.

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