Cannabinoid-Opioid Interaction in Chronic Pain, A Review

Everyone knows that cannabis delivers various medical benefits, perhaps the most important one being pain relief.  Other drugs relieve pain, and doctors normally prescribe opiates or opioids to relieve severe pain.  However, opioid side effects include sedation, nausea and vomiting, and addiction.

Nevertheless, the medical and cannabis communities have good cause to learn more about the combined use of cannabis and opioids.  Research has shown that cannabis enhances the pain relief of opioids while reducing nausea (Narang, 2008).  Patients may benefit from the cannabis-opioid combination by being able to reduce their use of the opioids and the side effects they cause.  Many patients already augment their opioid pain relief regimen with cannabis, so the interaction deserves close examination.

For some patients, psychoactivity poses the most serious side effect of cannabis.  Beyond that, patients can safely obtain pain relief from cannabis precisely because it has few other side effects.  The inherent safety of THC is due to the scarcity of cannabinoid receptors in the parts of the brain that control metabolism and breathing.

In 2010, Dr. Donald Abrams conducted a study using 24 patients at the San Francisco General Hospital.  The patients normally consumed morphine or oxycodone for significant pain due to various conditions (cancer, multiple sclerosis, migraine, etc.).  The study examined the subjective effects on the patients following the addition of inhaled cannabis vapor to their opioid regimen.  The patients inhaled vaporized cannabis three times a day for five days.  The patients also continued their prescriptions of sustained release tablets of morphine or oxycodone.

The authors justifiably proclaim that “This is the first human study to demonstrate that inhaled cannabis safely augments the analgesic effects of opioids.”  Indeed, this area deserves much more research.

The study found that cannabis reduced pain 40% on the first day, and after 5 days continued to reduce pain 27%.  The patients treated with the cannabis-morphine combination experienced more consistent pain relief than the patients that received the cannabis-oxycodone combination.  Cannabis and morphine pain reduction continued at about 33% throughout the 5 day trial.  In contrast, cannabis and oxycodone pain reduction dropped from 44% to 21% by Day 5.

The “high” felt on the first day dropped to a tenth of the original level by Day 5 for morphine, and dropped to a third of the original level by Day 5 for oxycodone.  Presumably, the patients taking oxycodone would experience still less of the high if the trial continued past five days. The fact that the high or the inebriation declines over time demonstrates the practical use of cannabis with opioids.  Patients who dislike the high can merely get past the first few days to enhance their opioid with a minimum of “impairment.”  In time, perhaps no feeling of inebriation would remain.  If that is true, higher doses of cannabis could provide even greater relief, and a greater reduction in opioid consumption.  Given the need to improve pain management and the absence of cannabis toxicity, much more work with cannabis is merited.

Cannabinoids and opioids share the effects of pain reduction, sedation, lowered body temperature and lowered blood pressure.  THC slows gastrointestinal motility and thus can slow the absorption of orally administered drugs. THC also seems to help certain drugs to get into the brain, perhaps because of the vasodilation (temporary thinning of the blood vessel walls).  The vasodilation effect of THC causes the reddening of the eyes as the eye capillaries enlarge.

As the reader may expect, a five-day trial can only provide a near-to-moderate time frame in which to observe effects.  The study also could have been limited by only using vaporization as the means of consumption.  The study made no attempt to avoid a placebo effect.  In general, studies that involve vaporizing or smoking cannabis cannot employ blind or double blind methods because of the “high.”

The study only used 24 volunteers, a number below that needed to generate good statistics.  Reliable statistics generally require a sample size of thirty or more.  Below thirty, statistical findings cannot establish confidence levels above 90 percent.  Nevertheless, small clinical studies provide the direction for larger, better funded studies.

Still another weakness related to the timing of two drug effects.  Inhaling THC produces a rapid and strong blood concentration while consuming opiate orally produces a maximum effect an hour or three after ingestion.  Indeed, another study (Narang, 2008) tested opioids with oral THC (synthetic Dronabinol) and this study also demonstrated significant decreases in chronic pain.

For the purposes of relieving pain alongside opioids, orally administered THC may be preferred by some patients over inhaled THC.  On the other hand, oral consumption of THC suffers from decreased control over the dosing, absorption being strongly affected by the types of food consumed and by patient metabolism.

Other issues worthy of comment include the following:  Some research indicates that cannabinoids increase endorphins, the neurotransmitters that opioids mimic.  And yet, research has clearly distinguished the CB1 and CB2 receptors (cannabinoid receptors) as being entirely different from those affected by opioids.  The interactions of CBD or other cannabinoids with opioids remains unexplored and will surely yield very exciting discoveries.

It is important to reinforce the finding that even within a week, the psychotropic effects of the THC decreased much more than the pain-relieving effects.  In the near absence of toxicity, the THC dose can be safely increased to compensate for the reduction in the “high.”  The few patients who dislike the THC inebriation can expect to get improved pain relief without the high after a few days.

In summary, this study provides an important benchmark in showing the value of inhaled THC to help opioids relieve pain.

Abrams, D. I., et. al. Cannabinoid-opioid interaction in chronic pain.  Nature 90:6, 844-851 (Dec 2011). Narang, S., et. al. Efficacy of Dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. J. Pain 9,254-264(2008).
article source: http://www.nature.com/clpt/journal/v90/n6/full/clpt2011188a.html

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