Accurate Education – Medical Marijuana – Cannabinoids & Opioids

Medical Marijuana – Cannabinoids & Opioids

The medical information on this site is provided as a resource for information only, and is not to be used or relied upon for any diagnostic or treatment purposes and is not intended to create any patient-physician relationship.  Readers are advised to seek professional guidance regarding the diagnosis and treatment of their medical concerns.


Impact of Medical Marijuana Use on the Use of Opioids – Overview

Historically, opioids have been the backbone of pain management. Due to the growing concern in recent years regarding the complications of opioid use for pain, there is a growing and at times a desperate effort to identify alternative means of treating pain that would have a better safety profile. Marijuana has been used for the management of pain for 4000 years, with pain being a major indication for cannabis medicines in Western society between 1842 and 1942.


Questions have been raised as to the effect that the use of medical marijuana and cannabinoids may have on both the use and the effectiveness of opioids, especially regarding the potential benefits and harms associated with the use of both agents together. Research on these topics is limited but is explored below.



Marijuana – Legislative Update for Louisiana

Marijuana – Medical Use Overview

“Medical Marijuana” – Getting Started

Marijuana vs Hemp


Cannabis-Based Medications:

Over-the-Counter Cannabinoid Medications:

Cannabidiol (CBD) – Introduction

Cannabidiol (CBD) – Clinical Use

Cannabidiol (CBD) – Drug Actions & Interactions


Prescription Cannabis-Based Medications:

FDA-Approved Prescription Cannabis-Based Medications

Louisiana Prescription Cannabis-Based Products – “Medical Marijuana”


Clinical Applications of Cannabis:

Cannabis – Anxiety (coming soon)

Cannabis – Chronic Pain Overview

Cannabis – Fibromyalgia

Cannabis – Headaches (coming soon)

Cannabis – Inflammatory Bowel Disease (coming soon)

Cannabis – Neuroinflammation (coming soon)

Cannabis – Sleep (coming soon)


The Medical Science of Cannabis:

The Endocannabinoid System

Marijuana – Botanical

Marijuana – Pharmacokinetics

Marijuana – Inhaled (Smoked and Vaporized)

Marijuana – Cannabinoids and Opioids


Cannabinoids and Terpenes:

Cannabinoids & Terpenes – An Overview (coming soon)


Marijuana – Cannabidiol (CBD)



Terpenes – An Overview (coming soon)


See also:

Marijuana – Discontinuing Use

Marijuana Addiction – Cannabis Use Disorder (CUD)


Key to Links:

Grey text – handout

Red text – another page on this website

Blue text – Journal publication



Marijuana (Cannabis) & Opioids

A Word of Caution

Regarding data gained from currently available research on the medical use of cannabis, it should be noted that research on “medical marijuana” is compromised by a lack of consistant marijuana product being evaluated. Because most studies are not performed in populations using consistent marijuana products with respect to dose, cannabinoid constituents and constituent ratios, the accuracy and application of conclusions related to the research is limited. Many studies are performed using experimental pain models in which volunteers are subjected to pain in an experimental setting rather than evaluating clinical pain in patients with chronic pain. Furthermore, it is likely there may be inherent bias in reported data collection from cannabis users who have personal opinions reflecting cannabis use.


These studies often do not offer the benefit of double-blind studies in which neither the subjects nor the researchers know the actual content of the drugs used which helps eliminate the bias introduced by either the subjects or the researchers. Given these limitations however, the following information is presented to encourage better informed decision making regarding the use of medical marijuana and related cannabinoids along with opioids.


Socioeconomic Impact of Medical Marijuana Use on the Use of Opioids


With the legalization and increased access to the use of marijuana medicinally in many states over the last decade, researchers have looked at the impact of the use of marijuana for pain on the use of opioids. Recent studies have shown that medical cannabis laws have resulted in significant (up to 33%) reductions in opioid-related causes of death and opioid usage. In addition, it has been noted there have been reductions in the number and cost of prescription medications used by Medicare patients, suggesting that some patients use cannabis as a substitute for various conventional pharmaceutical treatments.


A study published in 2017 evaluated the association between enrollment in the New Mexico Medical Cannabis Program (MCP) and opioid prescription use. By the end of the 21 month observation period, MCP enrollment was associated with 17 times higher odds of discontinuing opioid prescriptions, 5 times higher odds of reducing daily prescription opioid dosages, and a 47 percentage point reduction in daily opioid dosages. In this study, over 80% of the MCP subjects reduced their daily opioid prescription dosages, and over 40% stopped filling opioid prescriptions altogether within 1.5 years of starting use of medical marijuana.


Does the Use of Medical Marijuana Contribute to Opioid and/or Other Drug Abuse/Addiction?

A 2015 publication evaluated medical cannabis users who used or did not use opioids, to gain an understanding whether concurrent use of cannabis and opioids is associated with more serious forms of alcohol and other drug involvement. Those medical cannabis users who used opioids tended to be older with higher levels of pain and lower levels of functioning. However, no significant difference was found between medical cannabis users who used or did not use opioids with either lifetime or past-3-month use of other drugs, including alcohol, cocaine, sedatives, street opioids, and amphetamines. Also, medical cannabis users who used opioids rated the effectiveness of cannabis higher than opioids for pain and indicated a strong desire to reduce use of opioids. As explored further below, there appears to be a synergistic analgesic effect with the combination of opioids and cannabinoids providing greater analgesic benefit than either cannabis or opioids alone.


Pharmacology of Cannabis and Opioids

Synergism Between Opioids and Cannabinoids

There appears to be a synergistic analgesic benefit when cannabis is added to opioid treatment for pain in which there is a decrease in the lowest effective pain-relieving opioid dose (i.e., an opioid-sparing effect). Studies indicate a trend towards reduced use of opioids when patients taking opioids add cannabis to their regimen. Reports indicate that it is not uncommon for patients started on cannabis to be able to taper off opioids. However, there is a lack of quality research to evaluate these reports.


The mechanism(s) that allow for this synergism is unknown . CBD has been described as a modulator of μ and δ opioid receptors; there are, however, no studies demonstrating this behaviorally. The mechanism(s) may be due to THC activation of kappa opiate receptors. It has also been suggested that the cannabinoid–opioid interaction may occur at the level of their signal transduction mechanisms.


Preclinical Study Evaluating Synergy Between Morphine and a CBD-2 Agonist

A 2017 preclinical study showed for the first time that morphine and a CB2 agonist, JWH015 (like CBD) interact synergistically to suppress inflammatory, post-operative, and neuropathic pain. Furthermoe, the synergy extends to preventing opioid-induced reward behaviors in animals, suggesting that CBD may reduce abuse risk when taken with opioids. Additionally, the combination of morphine with the CB2 agonist reduces constipation associated with morphine. The authors conclude that their data support the use of opioid-CB2 combination therapy in treating chronic pain while limiting abuse liability.


 Oral Oxycodone and Smoked THC

A small 2018 study evaluating the combined use of low dose oxycodone 2.5-5 mg) along with smoked cannabis (5.6% THC) in an experimental pain model found a synergistic analgesic benefit with the combination.


Oral Morphine, Oral Oxycodone and Vaporized THC

A small 2011 study evaluating the combined use of oral morphine ER dosing (average 62mg, ranging 10-200mg twice/day) or oral oxycodone ER dosing (average 53mg, ranging 10-200mg twice/day)along with vaporized THC found a synergistic analgesic benefit with the combination. This study evaluated clinical pain in chronic paint patients.


Mean plasma THC levels in the subjects were 1.8 ng/ml at baseline, 126.1 ng/ml at 3 min, 33.7 ng/ml at 10 min, 10.9 ng/ml at 30 min, and 6.4 ng/ml at 60 min. The peak THC concentration occurred at 3 min in all the participants and THC plasma levels did not vary significantly by opioid group nor did the supplementation with THC affect the subjects opioid levels.


Morphine and Oral THC

Another small 2006 study evaluating the combined use of morphine 0.02 mg/kg intravenously along with 5mg oral THC in an experimental pain model found a synergistic analgesic benefit with the combination.




Opioid Tolerance

Interestingly, animals studies suggest that use of cannabis may reduce the development of tolerance to the analgesic benefits of opioids, resulting in less need for opioid dose escalation.


Cannabis, Opioids and Overdose Risk

There is no enhancement of cardiorespiratory suppression from opioids with the addition of cannabinoids due to the very low density of cannabinoid (CB) receptors in brainstem cardiorespiratory centers. However, while there is no increased risk of fatal overdose when combining cannabinoids with opioids, both classes of drugs share adverse clinical effects including sedation and cognitive impairment that can be additive when taken together. Caution is advised when taking these two classes of medications together.


Cannabis, Opioids and Metabolic Interactions


CBD has been identified as a potent inhibitor of the liver enzyme CYP2D6 which may have significant impact on the metabolism of opioids that are broken down by CYP2D6, including hydrocodone (Norc0, Vicodin, Zohydro, Hysingla), tramadol and codeine. As such, use of CBD with tramadol, codeine or hydrocodone may significantly reduce the analgesic effectiveness of these opioids.



National Academy of Sciences

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

This website appears to be good resource for exploring medical marijuana.



Cannabinoids & OpioidsConsequences of Medical Marijuana and Opioid Use

  1. It is premature to expand access to medicinal cannabis in hopes of solving the US opioid crisis – 2018
  2. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  3. Patterns and correlates of medical cannabis use for pain among patients prescribed long-term opioid therapy. – PubMed – NCBI
  4. Associations between medical cannabis and prescription opioid use in chronic pain patients – A preliminary cohort study – 2017
  5. The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature. – PubMed – NCBI
  6. The use of cannabis in response to the opioid crisis: A review of the literature. – PubMed – NCBI
  7. Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999–2010 – 2014
  8. Rationale for cannabis-based interventions in the opioid overdose crisis – 2017
  9. Cannabis and the Opioid Crisis – 2018
  10. Effects of Legal Access to Cannabis on Scheduled II-V Drug Prescriptions. – PubMed – NCBI
  11. Association of Medical and Adult-Use Marijuana Laws With Opioid Prescribing for Medicaid Enrollees. – PubMed – NCBI
  12. The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature. – PubMed – NCBI – 2009
  13. Experience of adjunctive cannabis use for chronic non-cancer pain: findings from the Pain and Opioids IN Treatment (POINT) study. – PubMed – NCBI 2015


Cannabinoids & Opioids – Pain

  1. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. – PubMed – NCBI
  2. Cannabinoid–Opioid Interaction in Chronic Pain
  3. Synergistic interactions between cannabinoid and opioid analgesics. – PubMed – NCBI
  4. Synergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine – 2006
  5. Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists – 2017


Cannabinoids & OpioidsOpioid Drug Interactions

  1. The Effect of CYP2D6 Drug-Drug Interactions on Hydrocodone Effectiveness – 2014
  2. Cannabidiol, a Major Phytocannabinoid, As a Potent Atypical Inhibitor for CYP2D6 – 2011


Cannabinoids & OpioidsImpact on Drug Abuse

  1. Use-of-Prescription-Pain-Medications-Among-Medical-Cannabis-Patients 

Emphasis on Education


Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.


For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.


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