A 2017 systematic review and meta-analysis summarized available pre-clinical research as “robust evidence of the opioid-sparing effect of cannabinoids” (Nielsen et al., 2017). Among the reviewed research, a mouse model of pain showed a 22.3-fold increase in pain relief with morphine & THC vs. morphine & control, while another found a 12.6-fold increase in efficacy of Hydromorphone when administered with THC (Smith et al., 1997, Cichewicz et al., 1998). The mechanism of action for this synergy is hypothesized to involve slowing the absorption of opioids via slowed gastrointestinal motility, which results in reduces necessary dosage and may reduce tolerance-building and side effects (Abrams et al., 2011).

A wealth of rodent research has established that Δ9-THC exposure during morphine withdrawal in mice reduced multiple withdrawal symptoms in addition to preventing tolerance to morphine effects (Frederickson et al., 1976, Vela et al., 1995, Lichtman et al., 2001, Valverde et al., 2001, Del Arco et al., 2002). Additionally, animal models suggest that both of the body’s naturally occurring endogenous cannabinoids (2-Arachidonoylglycerol [2-AG] & Anandamide [AEA]) reduce opioid withdrawal symptoms in rodents (Vela et al., 1995, Yamaguchi et al., 2001).

The mechanism of action for this synergy is hypothesized to involve slowing the absorption of opioids via slowed gastrointestinal motility, which results in reductions in the necessary dosage and may reduce tolerance-building and side effects.
Abrams et al., 2011

Clinical research in human patients has also exhibited promising results; studies have demonstrated significant opioid-reduction in chronic pain patients concurrently using cannabis, with one study reporting a 64% reduction and another a 44% reduction in opioid medications taken (Boehnke et al., 2016, Haroutounian et al., 2016). The 2017 Nielsen meta-analysis & literature review found the effective dose (ED50) of morphine + THC to be 3.6x lower than the ED50 of morphine alone (Nielsen et al., 2017). Furthermore, a large survey (n = 2897) of medical cannabis patients showed 97% (n=828) of the pain patients “strongly agreed/agreed” that they were able to decrease their amount of opioids used for pain (Reiman et al., 2017). Moreover, a 2015 study showed cannabinoids in tandem with opioids resulted in significant reduction in symptoms, increased quality-of-life, reduced pain, & reduced opioid usage when compared to opioids alone for pain (Degenhardt et al., 2015).