Cannabis legislation fails to protect Canada’s youth

Medical marijuana: Is it really time to lighten up?

I would like to respond to the thoughtful article, - Cannabis legislation fails to protect Canada's youth by Diane Kelsall, MD MEd CMAJ May 29, 2017 189:E737-E738; doi:10.1503/cmaj.170555

As a physician with almost 30 years of dealing with chronic pain, substance dependence and patients with mental health care needs, I have a great concern with the premise of this article on several grounds.

Distinguishing between chronic pain and concomitant substance abuse and substance dependence alone, is very difficult. It usually requires multiple visits with a thorough history of the patient's symptoms, detailed analysis of all the treatment modalities used thus far, diagnostic exam results, determination of a patient's addiction potential, and a detailed physical exam correlating the pathology as presented historically and by the diagnostic examinations. This historical data should be provided by the referring physician before the patient's appointment. This evaluation in itself may take more than one visit.

Treatment history may have involved the use of NSAID's, full dose acetaminophen ( one gram QID), muscle relaxants, chiropractic and physiotherapy, hydrotherapy, acupuncture, steroid or analgesia injection, cognitive behavioural therapy, spinal cord stimulator, TENs and psychiatric treatment. (The latter will be discussed later in this article.) Many times these referred patients have not used all of these treatments and can avoid use of opioids or MMJ.

Many different drugs can be used in the treatment of pain other than opioids. Methadone which is most often used for opioid addiction also has potent analgesic effects, ten times the potency of morphine. This has to be administered by a physician well versed in the use of this drug and who possesses s special dispensation with Health Canada. Often a stigma is associated with Methadone use, affecting patients who are taking it, but proper education and support can make long term treatment with the goal of slow weaning off the dose over an extended time, possible.

The combination of Duloxetine and Pregalbin synergism has been approved for the treatment of challenging pain syndromes such as fibromyalgia and neuropathic pain. Although not validated by convincing studies, this combination has anecdotally resulted in the relief of nerve pain as a result of degenerative disk disease of the lumbosacral spine. The mechanism of the synergy of these two drygs has not been identified. Many patients who have been on opioids can be switched to this drug combination, but knowledge regarding slow dose escalation to avoid side effects and close support of these patients is necessary.

Suboxone is a combination of the the opioid Buprenorphine and the potent opioid antagonist Naloxone. The drug may be used in substance dependence treatment but can also be used in treating chronic pain in substance dependent patients, and also in non-addicted individuals. This drug is a good choice for the treatment of chronic pain as it has a much lesser risk of substance dependence than other opioids.

Before MMJ or any opioid is prescribed, a thorough addiction assessment using well validated tools needs to be done. The Addiction Society of America (ASAM) website has multiple tools available to assess this risk. (1 )

Some present MMJ practices involve patients seeing the MMJ physician on their initial visit with prescriptions written for up to three months at a time, without the thorough consultation above. The patient with the licenced grower decides the ratio of THC:cannabinoid (CBD) over three months, often selecting for higher THC amounts, which result in greater neuropsychiatric effects welcome to patients who like to have "a high". This component also has less analgesic properties that CBD. The prescribing physician does not have an input on the route of MMJ (inhaled, edibles, oils, topical), side effect management and addictive potential of the MMJ prescribed for three months. For example, higher THC concentrations result in a higher risk of mental health problems, psychosis and memory difficulty. These side effects can be avoided by using higher CBD amounts with lower THC concentrations.(2) Each patient's response to equianalgesic amounts and route of administration can result in very different outcomes. This is also not controlled by the prescribing physician for ninety days.

Despite widespread availability, most clinical trials involving marijuana are using pharmaceutical CBD. The dose of THC provided by most licenced producers is significantly higher than the concentration used in current studies. Inhaled use shows no superiority in studies versus intranasal routes, with dose variability and unforeseen individual response possible as previously noted.(3) These issues as previously stated are not addressed for prolonged periods of time post initial prescription in some current practices.

Fishbain et al. have done a review of studies of chronic pain patients with seven studies showing the prevalence percentages for the diagnoses for drug abuse, drug dependence, and drug addiction were in the range of 3.2-18.9%.?(4)

In another study of prescription opiate abuse in chronic pain patients Thirty-four percent (26/76) met one, and 27.6% (21/76) met three or more of the abuse criteria. (5 )

Substance dependence before, during and after MMJ treatment is common. In this study, the odds of marijuana abuse/dependence were 1.81 times higher (95% CI: 1.22, 2.67; p=0.0040) among residents of states that had legalized medical marijuana.(6?) This study notes the role that policy changes and community norms about substance use play in shaping marijuana use and abuse/dependence. Future studies are also needed on the consequences of increased marijuana use, such as accidents, aggression, school drop out, psychosis, HIV and sexually transmitted disease rates. (7, 8, 9)

All of these references emphasize the need for addiction potential assessment of chronic pain patients before and during MMJ treatment. In addition, they illustrate that up to 30% of opioid users referred for MMJ treatment are substance dependent and therefore not candidates for MMJ.

Chronic use of marijuana and therefore MMJ, can result in many side effects some of which can be permanent. Adverse effects of cannabis may vary widely among and within individuals depending on dose, administration route, social and physical setting of drug use, individual dose response and user expectation. Adverse side effects may be divided into acute and chronic.(10) Acute consequences of MMJ use can be: psychological effects, such as anxiety, dysphoria, paranoia, agitation, or psychotic symptoms (more common with ingestion of high doses)

cognitive and psychomotor impairment, such as reduced concentration, short-term memory, information processing, and reaction time that may cause?functional impairment?and increased risk of motor vehicle crash. Road test trials have indicated that patients smoking marijuana swerve in and out of lanes related to dosage. Common concomitant alcohol use worsens reaction time and lane changing. Huge education campaigns must be developed to dispel the myth that cannabinoid-impaired driving is less a risk than driving after alcohol use.(11)

acute?cardiovascular effects, such as increases in heart rate and blood pressure

pulmonary effects, including acute bronchodilation

Adverse effects with long-term or daily use of cannabis may include cardiovascular effects, such as decreased heart rate, reduced blood pressure, or orthostatic hypotension pulmonary effects, such as increased risk of cough, phlegm, and wheezing, as well as other respiratory complications. ?However, differing patterns of inhalation mean that smoking a 'joint' of cannabis results in exposure to significantly greater amounts of combusted material than with a tobacco cigarette. The histopathological effects of cannabis smoke exposure include changes consistent with acute and chronic bronchitis. Cellular dysplasia has also been observed, suggesting that, like tobacco smoke, cannabis exposure has the potential to cause malignancy. These features are consistent with the clinical presentation. Symptoms of cough and early morning sputum production are common (20-25%) even in young individuals who smoke cannabis alone. Almost all studies indicate that the effects of cannabis and tobacco smoking are additive and independent. Public health education should dispel the myth that cannabis smoking is relatively safe by highlighting that the adverse respiratory effects of smoking cannabis are similar to those of smoking tobacco, even although it remains to be confirmed that smoking cannabis alone leads to the development of chronic lung disease.(12)

cannabinoid hyperemesis syndrome (CHS), which is characterized by severe recurrent nausea and vomiting, particularly in the morning hours

long-term?neurocognitive deficits

cannabis use disorder (CUD) is continued problematic use despite negative consequences that causes significant distress or impairment in functioning. It typically includes a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal state. The reference quoted details this very important consequence of long term use of MMJ in greater detail. (13)

- CUD occurs in about 10% of individuals overall who use cannabis

25%-50% of individuals who use cannabis daily are reported to develop CUD

cannabis use during adolescence may be associated with increased likelihood of CUD

adolescents appear more vulnerable to brain-based negative effects

Some possible adverse effects are of concern, but have unclear evidence:

1. unclear effects of cannabis on?the endocrine system, but reported possible association with gynecomastia in males and infertility in men and women 2. inconsistent evidence regarding cannabis use and risk for?psychosis?or?mood disorders 3. inconsistent evidence associating cannabis and increased risk of cancer

Psychologic issues are present as the cause of chronic pain in an alarming number of patients, especially in women. A study done by Goldberg et al. showed that all pain groups had a history of abuse exceeding 48% : fibromyalgia, 64.7%; myofascial, 61.9%; facial, 50%; other pain, 48.3%. All groups had a history of family alcohol dependence exceeding 38%, and a history of drug dependence ranging from 5.8 to 19.1%. A combined history of pain, child physical abuse, and alcoholism was prevalent in 12.9 to 35.3%. Logistic regression showed patients who were female, with an alcoholic parent, using non-narcotic drugs were more likely to be members of the facial, myofascial, and fibromyalgia groups. This study shows that over 50% of patients with chronic pain had a history of abuse. (14)

In another study, the case histories of 100 patients in a multidisciplinary pain clinic were evaluated. 44% reported serious trauma long before the development of pain. This emphasizes that chronic pain is a complex, multidimensional phenomenon where medical intervention has often little effect due to the aforementioned psychological traumas not being treated along with pain symptom management.(15)

These and many other studies show that almost half of all patients, especially women, are dealing with pain that needs to be treated by a multidisciplinary team, for successfully addressing the etiology of the complex syndrome that is chronic pain. These needs cannot be addressed by a MMJ prescriber. However, treating with MMJ or opioids alone and not addressing the many psychological issues involved with chronic pain is a partial treatment of chronic pain at best.

In conclusion, MMJ alone, as has been advocated by this letter, leads to a higher incidence of substance dependence in a MMJ-treated patient population that are already much of the time, narcotic dependent at the presentation for MMJ consultation. Careful addiction risk histories should therefore eliminate about 30% of patients being referred for MMJ treatment.

Multiple studies also note that chronic, daily MMJ users develop a substance dependence or cannabis use disorder about 25-50% of the time. This dependence or abuse shocking figure is defined as per the criteria for CUD.

Relapse rates observed for cannabis use disorders are comparable to those for other abused drugs, and only 15-37% of patients undergoing psychotherapeutic and pharmacological interventions achieve continued abstinence.(16 ) As mentioned above, this high relapse rate is likely due to not treating associated psychologic etiologies in pain disorders.

CUD along with the many side effects of chronic use mandate MMJ users to not get prescriptions for marijuana on the first encounter with a physician, until the exhaustive evaluation described here be carried out. The initial and ongoing prescriptions should only be for one month as is the advice for chronic opioid users. Random and initial urine testing should be carried out to ensure drug compliance, prevent diversion and the concomitant use of other opiates. Drug contracts should be signed by the prescriber and patient with clear reasons for cessation of MMJ to be made clear.

The close monitoring for recognized dependence, cannaboid use disorder, acute and chronic side effects of MMJ and concomitant street drug use with MMJ, should be standard practice. The ratio of THC:CBD should be determined by a physician and not by licenced growers and patients who have secondary gain and no knowledge of all the medical consequences outlined in this statement.

Clear guidelines regarding the use of MMJ must be developed by the different levels of government and the physician regulatory authorities in each jurisdiction.

Finally, the endemic frequency of psychologic factors being the etiology of chronic pain must be addressed by a multidisciplinary team before and during MMJ treatment, to possibly even obviate the need for any type of opioid. This cannot be done by MMJ prescribers on their own.

The reality is that MMJ treatment may indeed have a place in a select number of patients. However, this extremely young and for a large part scientifically-invalidated treatment has to be much better defined before it is thought to be a panacea for treatment of all chronic pain patients. This needs to be carried out by valid science, physician regulatory body guidelines, government and closer monitoring of licenced producers.

Particularly worrisome is that the federal government is proceeding with plans for the decriminalization of smaller amounts of marijuana, not having considered the topics examined in this document.

It is hoped that the government will consider these issues before final legislation is passed that could harm an already marginalized patient population of chronic pain sufferers.

REFERENCES:

1. American Society of Addiction Medicine. Screening and Assessment Tools online. https://www.asam.org/education/live-online-cme/fundamentals- of-addiction-medicine/additional-resources/screening-assessment-for- substance-use-disorders/screening-assessment-tools

2. Panlilio L.F.,?Goldberg S.R. and Justinova, Z. Cannabinoid abuse and addiction: Clinical and preclinical findings.

Clin Pharmacol Ther. 2015 Jun; 97(6): 616-627.

3. Whiting P.F. et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73.

4. Fishbain, D.A. , Rosomoff, H.L. , Rosomoff, R.S. Drug abuse, dependence, and addiction in chronic pain patients. Clin J Pain. 1992 Jun;8(2):77-85.

5. Chabal, C. et al. Prescription opiate abuse in chronic pain patients: clinical criteria, incidence and predictors. Clin J Pain 1997 Jun;13(2):150-5.

6. Cerda, M. et al. Medical marijuana laws in 50 states: investigating the relationship between state legalization of medical marijuana and marijuana use, abuse and dependence. Drug Alcohol Depend. 2012 Jan 1;120(1-3): 22-27.

7. Fergusson DM, Horwood LJ, Swain-Campbell NR. Cannabis dependence and psychotic symptoms in young people.?Psychol. Med.?2003a;33:15-21.?

8. Fergusson DM, Swain-Campbell NR, Horwood LJ. Arrests and convictions for cannabis related offences in a New Zealand birth cohort.?Drug Alcohol Depend.?2003b;70:53-63. 9. Hall W, Lynskey M. The challenges in developing a rational cannabis policy.?Curr. Opin. Psychiatr.?2009;22:258-262.

10. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 912360, Adverse effects of cannabinoids; [updated 2017 Mar 12, cited? July 27, 2017]; Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=912360. Login Required.

11. Bondallaz. et al. Cannabis and its effects on driving skills. Cannabis and its effects on driving skills. Forensic Sci Int. 2016 Nov;268:92-102

12. Taylor D.R. and Hall W. Respiratory health effects of cannabis: position statement of the Thoracic Society of Australia and New Zealand 2003. Intern Med J 2003J ul;33(7):310-3

13. CANNABIS USE DISORDER online. http://www.mentalhealth.com/home/dx/cannabisdependence.html

14. Goldberg R.T., Pachasoe W.N. And Keith D. Relationship between traumatic events in childhood and chronic pain. Disability and Rehabilitation 1999; Vol. 21(1)

15. Bewll R.F., Schjodt B., Paulsberg A.G. Childhood trauma and chronic pain. Tidsskr Nor Legeforen 2000;120: 2759-60

16. Panlilio LV, Goldberg SR, Justinova Z. Cannabinoid abuse and addiction: Clinical and preclinical findings.?Clinical pharmacology and therapeutics. 2015;97(6):616-627.

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Conflict of Interest:

None declared