Despite not understanding the scientific mechanisms behind cannabis’ therapeutic value, it was used in ancient China, Israel, Greece, Rome, and India primarily to treat and relieve pain (Pacher et. al., 2006). While more research needs to be conducted, we now have a better understanding of the relationship between pain, the Endocannabinoid System (ECS), and cannabis therapies.

Numerous studies verify the integral role of the ECS in modulating various physio logical functions throughout the human body, including pain perception and inflammatory response (Behl et al., 2022).

CB1 receptors were found in areas connected to pain response in the brain, spinal dorsal horn, dorsal root ganglia, and peripheral afferent neurons (Dasram et al., 2022; Strangman et al., 1998). Via these receptors, phytocannabinoids produce antinociceptive effects on the central nervous system, spinal cord, and peripheral sensory nerves (Crocq 2020; De Petrocellis et al., 2009). Recent studies further indicate that cannabinoids are effective against both neuropathic and inflammatory chronic pain (Pacher et. al., 2006). specifically via the antihyperalgesic effects of cannabinoids on CB2 receptors.

CBD is frequently used to treat various types of acute and chronic pain due to its analgesic and anti-inflammatory effects.

CB1 receptors are located mainly within the CNS which is responsible for pain perception, and due to the allosteric activity CBD has on CB1, evidence shows CBD can be beneficial in managing chronic pain (Peng et al., 2022; Laprairie et al., 2015; Martínez-Pinilla et al., 2017). Furthermore, CBD produces anti - inflammatory effect s by serving as an antagonist to CB2 receptors, suppressing mast cell degranulation and boosting neutrophils within pain center (Pertwee, 2008).

Along with CB1 and CB2 receptors, studies have also shown CBD’s analgesic effects via its modulation of GPR2 (Ruiz-Media et al., 2011), serotonin 5-HT1A (Russo et al., 2005) and TRPV1 (Di Marzo 2004).

Studies have confirmed that CBD reduces the levels of pro-inflammatory cytokines, inhibits T-cell proliferation, induces T-cell apoptosis, and reduces migration and adhesion of immune cells (Sinemyiz et al., 2019; Petrosino et al., 2018).

Opioid addiction creates neurobiological changes within the brain by dysregulating motivation and reward pathways. Recent studies indicate that the Endocannabinoid System plays an integral role in the rewarding and motivation effects of not only cannabinoi ds, but of alcohol, nicotine, and opioids via endocannabinoid release in the ventral tegmental area (Maldonado et al., 2006)

Through self-reports and clinical rese arch, evidence shows cannabis has a significant positive impact on the reduction of opioid use, primarily due to substitution effect and the shared therapeutic properties of cannabinoids and opioids (Lucas, 2017).

Studies show a reduction in the use of opioids and prescription drugs used to treat pain, depression, anxiety, sleep disorders, nausea, seizures, and psychoses in states with medical cannabis pro grams (Bradford et al., 2016 ). In fact, there was a 24.8% lower mean annual opioid overdose mortality rate in U.S. states with medical cannabis laws compared to those without (Bachhuber et al., 2014). Another study indicated that cannabis reduced opioid use, decreased side effects of medications, and improved overall quality of life by 64% in chronic pain patients (Boehnke et al., 2016).

In an eight-week study on 72 chronic pain patients, 53% reduced or e liminated their opioids after adding CBD - rich hemp extract to their regimens. Almost all CBD users (94%) reported quality of life improvements, concluding that CBD could significantly reduce opioid use and improve chronic pain and sleep quality among patie nts who are currently using opioids for pain management (Capano et al., 2020).

Numerous studies indicate that most chronic pain syndromes, regardless of their origin, share comorbidities in whic h CBD has therapeutic value – primarily anxiety and irregular sleep (Dahan et al., 2014). Lack of sleep can increase pain sensitivity (Sivertsen et al., 2015) and anxiety disorders can cause physical symptoms such as heart - palpitations and exacerbate pain perception due to cognitive over - signaling of impending danger (Woo, 2010).