American Society of Regional Anesthesia and Pain Medicine May 2018 - 33

(THC) and cannabidiol (CBD), through which medical cannabis
participates in the ECS.4
THC acts on 2 well-defined G-protein-coupled receptors: CB1
and CB2. CB1 receptors are most common in the central nervous
system but also found in peripheral tissues; CB2 is a central and
peripheral neuronal and nonneuronal receptor that modulates
inflammatory and neuropathic pain.4,7 Therefore, medical cannabis
modulates pain at supraspinal, spinal, and peripheral levels,
by modifying pain transmission and inflammatory responses.
Interestingly, CB1 receptors are infrequently found in brain stem
respiratory centers, explaining a low risk of respiratory depression
from marijuana use.4
CBD, while producing some pharmacological effects similar to THC,
such as attenuating inflammation, does not work primarily through
CB1 or CB2 receptors. Instead, its anti-inflammatory, anxiolytic,
and antiseizure effects are likely mediated through one or several
other mechanisms, such as interactions with serotonin, adenosine,
glycine, or transient receptor potential channel receptors.
As mentioned, cannabis use has a low risk of respiratory
depression, and no lethal cannabis overdose has been reported in
humans to date.1,4 Cannabis use, however, does not come without
consequence. THC is a psychoactive analgesic that can have shortterm side effects on learning, memory, and attention, and it can
cause euphoria; long-term side effects are not yet established.8,9
Cannabis use before driving increases the risk of having a motor
vehicle accident. In addition, prescription of medical cannabis
to adults inadvertently exposes children to the risks from the
compound. Cannabis legalization may even decrease the perception
of its risks to adolescents, who have developing brains and are at
greatest risk for experimenting with substances of abuse.8
In a nationwide study in the United States, 10% of all adult
cannabis users reported taking the drug exclusively for medical
purposes, and 36% reported a mixture of recreational and medical
purposes.8 Accordingly, understand that the levels of individual
chemical constituents in most botanical cannabis products-and
consequently in medical cannabis products-are currently greatly
variable and unregulated.
Chronic pain conditions are common, debilitating, and notoriously
difficult to treat using opioids, nonsteroidal anti-inflammatory
agents, anticonvulsants, antidepressants, local anesthetic or steroid
injections, and nonpharmacologic methods.10 Medical cannabis
can act as an adjuvant agent for refractory pain, with meaningful
improvement in pain reported for 1 of every 3.5 to 9 patients with
chronic, noncancer pain.4,9,10
In 2017, the National Academies of Sciences, Engineering, and
Medicine (NASEM) released a comprehensive review of studies titled

Health Effects of Cannabis and Cannabinoids. The NASEM committee
found that chronic pain patients treated with medical cannabis can
experience a significant reduction in pain symptoms, short-term use
of synthetic oral cannabinoids improves multiple sclerosis-related
muscle spasms, and synthetic oral cannabinoids can prevent and
improve chemotherapy-induced nausea and vomiting.8
Patients with a variety of different diseases may someday benefit
from medical cannabis. The hundreds of natural components in
botanical cannabis should be studied, and novel, therapeutic,
cannabinoid-derived agents may be discovered. Many of our
present-day pain medications were actually derived from the plant
world, including opioids, salicylates, and capsaicin. Unfortunately,
cannabis's unyielding federal status as a schedule I drug continues
to limit effective research.
In 1994, California was the first state to legalize medicinal cannabis
use. Since the Rohrabacher-Farr amendment, medical cannabis
is now legalized in 29 states and Washington, DC. Our state of
Pennsylvania passed its legislation in April 2016 and continues to
solidify the rules and regulations. Pennsylvania's law has taken
a highly medicalized approach, requiring staffing of dispensaries
by physicians and pharmacists and the incorporation of funded
research collaborations between select medical cannabis entities
and the state's medical and research institutions. In addition,
clinicians involved in recommending and dispensing cannabis will
be required to complete at least 4 hours of continuing medical
education. Current indications for medical cannabis prescription
in Pennsylvania are 17 serious medical conditions, including pain
listed on its own, as well as amyotrophic lateral sclerosis, cancer,
Crohn disease, spinal cord injury, HIV/AIDS, inflammatory bowel
disease, multiple sclerosis, neuropathy, and sickle cell anemia.
As we await cannabis reclassification at a federal level, pain
physicians should leverage what we do know about cannabis
to benefit our patients with chronic pain. Only half of chronic
pain patients describe their pain as "under control."4 Until
blinded, randomized studies are conducted, pain physicians can
prescribe medical cannabis to patients whose pain is refractory
to conventional medical therapies. Institution of multimodal pain
regimens can be used to minimize medical cannabis dosages and
its potential side effects. Certainly, all patients should have the
opportunity to ease their unrelenting and debilitating conditions.
REFERENCES
1.

Bostwick JM. Blurred boundaries: the therapeutics and politics of medical
marijuana. Mayo Clin Proc. 2012;87(2):172-186.

Pertwee RG, ed. Handbook of Cannabis. 1st ed. Oxford, United Kingdom: Oxford
University Press; 2014.

Anderson DM, Hansen B, Rees DI. Medical marijuana laws, traffic fatalities, and
alcohol consumption. IZA Discussion Paper Series. 2011;6112:1-28.

Burns TL, Ineck JR. Cannabinoid analgesia as a potential new therapeutic option
in the treatment of chronic pain. Ann Pharmacother. 2006;40:251-260.

American Society of Regional Anesthesia and Pain Medicine
2018

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