Cannabidiol (CBD) and Opioid Addiction

Opioids provide effective analgesic relief against acute and chronic pain.  Rates of opioid prescription have skyrocketed over the past two decades and opioid addiction is extremely high among users reaching almost 50% (1, 2).  As opioid prescription and addiction rates rise, overdose deaths in the US have nearly tripled in the past 15 years (3).

Cannabidiol (CBD) is a non-psychoactive cannabinoid that has been reported to dampen the “reward properties” of drugs like cocaine, amphetamine and opioids in animal models (4, 5). Put simply, CBD might be able to block the urge of users to continue to use these highly addictive drugs.

In a recent study conducted at the University of Mississippi, Markos et al (6) injected separate groups of mice with either saline (control) or morphine in combination with different doses of CBD. The treated mice were then subjected to drug/no drug conditioning experiments.  The results from these experiments showed that morphine-conditioned mice displayed a robust preference for morphine. This robust morphine preference was significantly attenuated in mice that also received morphine plus CBD (10 mg/kg). Further, CBD (10 mg/kg) alone did not exhibit any rewarding or aversive properties in saline-conditioned mice. This finding is the consistent with the work of others who also found that CBD lacks psychotomimetic, aversive or reward properties (7-10).

Taken together, these results suggest CBD can block opioid reward behavior, i.e. deter the subsequent use of opioids, and may be useful as a treatment in opioid addiction treatment settings.  However, while these results may be encouraging, controlled, human clinical studies with CBD must be performed to determine whether or not the cannabinoid may be useful as a pharmacologic intervention to help treat opioid addiction.

References

  1. Dart RC, Surratt HL, Cicero TJ, Parrino MW, Severtson SG, Bucher-Bartelson B, Green JL. Trends in opioid analgesic abuse and mortality in the United States. N Engl J Med 2015; 372: 241–248
  2. Højsted J, Sjøgren P. Addiction to opioids in chronic pain patients: a literature review. Eur J Pain 2007; 11: 490–518
  3. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths – United States, 2010–2015. MMWR Morb Mortal Wkly Rep 2016; 65: 1445–1452
  4. Parker L, Burton P, Sorge R, Yakiwchuk C, Mechoulam R. Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmachology 2004; 175: 360–366
  5. Katsidoni V, Anagnostou I, Panagis G. Cannabidiol inhibits the reward facilitating effect of morphine: involvement of 5-HT1A receptors in the dorsal raphe nucleus. Addict Biol 2013; 18: 286–296
  6. Markos JR, Harris HM, Gul W, ElSohly MA, Sufka KJ.  Effects of cannabidiol on morphine conditioned place preference in mice. Planta Med 2017 12/13 DOI: 10.1055/s-0043-117838
  7. Parker L, Burton P, Sorge R, Yakiwchuk C, Mechoulam R. Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmachology 2004; 175: 360–366
  8. Katsidoni V, Anagnostou I, Panagis G. Cannabidiol inhibits the reward facilitating effect of morphine: involvement of 5-HT1A receptors in the dorsal raphe nucleus. Addict Biol 2013; 18: 286–296
  9. Mechoulam R, Parker L, Gallily R. Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol 2002; 42: 11S‑19S
  10. Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus L. Cannabidiol – recent advances. Chem Biodivers 2007; 4: 1678–1692

Companies Developing Cannabis-Derived Pharmaceuticals

There is a growing body of evidence that suggests that extracts containing multiple cannabinoids or a single cannabinoid can be developed as a pharmaceutical product to treat specific therapeutic indications.  There are a small number of companies that have announced their intentions in this space.  Rumor has it that many major pharmaceutical and biotechnology companies are quietly evaluating this business opportunity, but are reluctant to disclose their forays into the Cannabis space for legal and public relations reasons.

Below is a partial list of companies who are actively involved in development of Cannabis-derived pharmaceuticals.

I will update the table soon as there are lots of new startups that have entered the space in the past 6 months or so!

Company Product Properties Indication(s)
AbbVie Marinol® (dronabinol) Synthetic Δ-9-THC Chemotherapy-induced nausea/vomiting (CINV); MS neuropathic pain; HIV/AIDS appetite stimulate
Valeant Pharmaceuticals International Inc Cesamet®

(nabilone)

Synthetic Δ-9-THC Management of  nausea/vomiting
GW Pharma Sativex®

(naviximols)

Mixture of extracts of cannabis plant containing two cannabinoids in 1:1 ratio, Δ-9-THC and CBD (cannabidiol) in 50% alcoholic solution ; oro-mucosal delivery (mouth spray) Neurologic and cancer-related pain; Spasticity in patients with MS
Epidiolex® CBD (cannabidiol) liquid extract from genetically-defined cannabis strain Orphan pediatric epilepsy; Dravet Syndrome and Lennox-Gastaut syndrome
GWP42003 Not disclosed Ulcerative colitis
GWP42004 Not disclosed Type 2 diabetes
GWP42006 Cannabidivarin (CBDV) Adult epilepsy
Society for Clinical Research (Germany) Cannador® Oral capsule containing whole plant extract with standardized THC:CBD ratio of 2:1 Muscle stiffness; MS spasticity/pain; cachexia in cancer patients, post-operative pain management
Kannalife Not named Cannabis extract/semi-synthetic CBD (cannabidiol) Hepatic Encephalopathy
Aphios APH-080 Liposomal formulation of Δ-9-THC CINV; Appetite stimulant for HIV and cancer patients
APH-1305  CBG (cannabigerol) liposomal-oral delivery MS & other neuroinflammatory  neurodegenerative disorders
Cannabis Sciences CS-S/BCC-1 CBN (cannabinol) enriched extracts Oncology
CS-TATI-1 Plant extract Kaposi Sarcoma
Not Named CBN (cannabinol) plus other cannabinoids Anxiety, sleep disorders, Alzheimers disease
Medical Marijuana Sciences Not Named CBD (cannabidiol) extracts plus microencapsulation technology Brain and pancreatic cancer

Medical Marijuana Courses Are Now Available for College Credit!

Back in the day when I was going to graduate school in Madison, WI,  there was no such thing as medical Cannabis (although there was plenty of weed to go around).  But, as the line in that old Dylan song goes “the times they are a changin”

Late last month, the University of California-Davis announced that it would be joining Humboldt State University in offering undergraduate students a course entitled Physiology of Cannabis.  FYI, Humboldt State has been offering courses in medical Cannabis since 2012 (not surprising since the school is located in prime Cannabis cultivation territory).

According to UC-Davis officials the semester-long, three credit course will be aimed at biology students and will cover the endocannabinoid system, the effects of cannabinoids on the human body and the therapeutic value of Cannabis.

Likewise, Sonoma State University announced that it will be offering a one day symposium on March 11, 2017  to members of the healthcare industry in the Bay area. The symposium is entitled Medical Cannabis: A Clinical and it is intended as a workforce development course.  Nurses, physicians and pharmacists can get continuing education credit for the course. Topics that will be covered include the history of cannabis, an introduction to cannabinoids and terpenes, dosing and administration of cannabinoids, legal implication and other medical-related issues. The university is also planning a three day course on Cannabis regulatory issues later in the month.

While these courses are available, there is currently no undergraduate degree program in Cannabis science/medicine offered by any US university or college. That said, don’t be surprised if this major becomes a reality in States where medical and recreational Cannabis are legal.