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Cannabis for Pain: Clinical & Animal Evidence

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Cannabis for Pain: Clinical & Animal Evidence Study

A September 2023 study entitled "Cannabis Constituents for Chronic Neuropathic Pain; Reconciling the Clinical and Animal Evidence" that was published in the Journal of Neurochemistry explored how "recent preclinical studies have predicted the clinical limitations of THC-containing cannabis extracts, and importantly, point to how they might be improved."

A man in pain holds up his hand
Does cannabis treat pain?

Reported the study: "Nociceptive or acute pain is an adaptive, neuroprotective and short-lived sensation that promotes the survival of an organism by producing behavioural adaptations that act to prevent potential or ongoing injury. Chronic pain, often viewed as a maladaptive response, is identified as pain that lasts beyond the expected time required for normal tissue healing, typically 3–6 months. It affects up to 40 percent of U.S. adults and is estimated to cost $560 billion [every year] in lost productivity and medical treatment."

Cannabis for Pain: Clinical & Animal Evidence Study Conclusions

Cannabis for Pain: Clinical & Animal Evidence Study. The study's authors concluded the following:

"The current meta-analysis evidence for the clinical use of cannabis extracts in the treatment of chronic neuropathic pain is not encouraging and is difficult to reconcile with the large body of positive evidence from pre-clinical animal neuropathic pain models.

"When assessing clinical effectiveness, there is little data on comparisons between the different types of cannabis extracts (THC, CBD and nabiximols), dosing regimens (dose level and duration of treatment and route of administration) and targets. These factors are important because there are emerging signals from the pre-clinical animal studies that provide a rational basis for the poor clinical effectiveness observed for cannabis-based medicines (CBMs) and potential clues as to how they might be refined.

"The clinical issue is that these THC-containing extracts do not provide a more effective treatment option for chronic neuropathic pain than placebo."

"Clinical evaluation has largely been restricted to THC-containing medicines, either cannabis, THC alone (or its synthetic derivatives) or nabiximols (THC:CBD combinations, such as Sativex). The clinical issue is that these THC-containing extracts do not provide a more effective treatment option for chronic neuropathic pain than placebo and that they are generally associated with the typical cannabis-like side effects.

"This is reflected in the pre-clinical animal work where direct injection of THC reduces allodynia in many neuropathic pain models with high effectiveness, but only at doses where substantial cannabinoid-like side effects are observed. Injected nabiximols only produce modest reductions in allodynia at low side effect-free doses but are indistinguishable from THC at higher doses. Furthermore, oral nabiximols display little to no analgesic synergy and therefore have no advantage over THC.

A man with a knee injury in physical therapy.
Marijuana may help pain.

"These issues arise because higher doses of THC-containing medicines (THC alone and THC:CBD combinations) produce pain relief and side effects via a common target, cannabinoid CB1 receptors. These issues reflect many of the problems observed in clinical studies on THC-containing CBMs. Thus, it is essential to distinguish between different THC-containing formulations, including their dosing and routes of administration, in terms of their activation of cannabinoid CB1 receptors.

"On the contrary, CBD alone appears to provide a potentially safer alternative because it reduces the allodynia associated with many neuropathic pain models without the cannabis-like side effects associated with THC. Importantly, its effectiveness increases with chronic treatment. This greater safety is likely because of the lack of involvement of cannabinoid CB1 receptors.

"CBD has a potentially safer alternative because it avoids the cannabis-like side effects associated with THC."

"The current animal literature therefore highlights the potential importance of CBD as a therapeutic tool against neuropathic pain, particularly with long-term treatment, either alone or as an adjuvant to current drugs. However, CBD has lower effectiveness than THC-containing drugs. It also undergoes rapid and variable metabolism making it more difficult to assess, particularly with oral administration.

"To determine the optimal approach, pre-animal research on CBD is needed, particularly on its non-cannabinoid CB1 receptor-related mechanisms of action. This is crucial in determining the direction of future clinical research into these CBMs, particularly the potential of CBD as an alternative treatment option.

View the original study.

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