Intro: On May 29, 2014, the Governor of Minnesota signed the medical cannabis therapeutic use law: 2014 Minnesota Laws chapter 311. This Act is designed to enable truly sick patients to engage in the therapeutic use of cannabis while preventing it from being misused or diverted from its medical purpose.
Their report summarizes clinical trials and prospective observational studies in humans, published in peer reviewed journals, which focus on medical cannabis formulations consistent with Minnesota’s medical cannabis program. It is produced in fulfillment of Minnesota Statutes Section 152.25, subdivision 2. The report was first produced in December 2014, and it is updated annually by the Minnesota Department of Health Office of Medical Cannabis.
The report contains studies on the medical conditions identified in the statute for inclusion in Minnesota’s medical cannabis program and they are: Severe or chronic pain; Nausea or severe vomiting; cachexia or severe wasting; Glaucoma; Human immunodeficiency virus or acquired immune deficiency syndrome; Tourette’s syndrome, Amyotrophic lateral sclerosis, Seizures, including those characteristic of epilepsy, Severe and persistent muscle spasms, including those characteristic of multiple sclerosis, Crohn’s disease (expanded to Inflammatory Bowel Disease in 2016); Terminal illness; Cancer.
The first of a six-part series – this article will focus on Sleep Apnea
Description: Obstructive sleep apnea (OSA) is a sleep disorder characterized by repetitive episodes of complete (apnea) or partial (hypopnea) collapse of the upper airway (mainly the oropharyngeal tract) during sleep, with a consequent cessation/reduction of airflow. The obstructive events cause a progressive asphyxia that increasingly stimulates breathing efforts against the collapsed airway, typically until the person is awakened. These episodes cause acute physiological disruptions including fragmented sleep, intermittent hypoxia, and exaggerated fluctuations in heart rhythm, blood pressure, and intrathoracic pressure. Over time, the acute disruptions lead to chronic conditions such as hypertension and heart disease, reduced cognitive function, depression, and impaired performance at work and while driving, as well as premature death.
One randomized, placebo-controlled clinical trial of cannabis or a cannabinoid product has been published (Carley 2018). This six-week trial of dronabinol (synthetic THC) at doses of 2.5 mg and 10 mg daily, taken at bedtime, found a modest treatment benefit from dronabinol with substantial variation among patients in degree of response. The authors’ responder analysis suggests only a portion – likely a rather small portion – of OSA patients receive a clinically meaningful reduction in AHI from the therapy used in this trial. Carley DW, Prasad B, Reid KJ, Malkani R, Attarian H, et al. Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial: Effects of dronabinol in obstructive sleep apnea. Sleep Jan 1;41(1). doi: 10.1093/sleep/zsx184
Deeper Dive: By random assignment 73 adults with moderate or severe obstructive sleep apnea (OSA) received either placebo (n=25) or 2.5 mg dronabinol (n=21) or 10 mg dronabinol (n=27) daily, one hour before bedtime for 6 weeks. Participants randomized to the 10 mg/day dronabinol group received 2.5 mg/day for the first seven days, then 5.0 mg/day for seven days before reaching final dosage of 10 mg/day.
Inclusion criteria included:
apnea/hypopnea index (AHI) ≥15
≤50 documented by screening polysomnography (PSG).
Extensive exclusion criteria included:
non-invasive treatment for OSA within one month (self-report);
Epworth Sleepiness Scale (ESS) score <7 (to exclude non-sleepy subjects);
body mass index (BMI) >45; motor vehicle accident or “near-miss” due to sleepiness (self-report) within 2 years;
arterial oxygen saturation <75% for more than 5% of total sleep time on baseline PSG;
severe OSA that in the investigator’s judgment precluded delaying (re)institution of positive airway pressure treatment;
use of CNS active drugs; recreational drug use or positive urine drug screen.
Important Keys:
At baseline, average AHI was 25.9±11.3, ESS score was 11.45±3.8, maintenance of wakefulness test (MWT) mean latency was 19.2±11.8 min, BMI was 33.4±5.4 kg/m2 and age was 53.6±9.0 years.
The number of adverse events and treatment adherence (0.3±0.6 missed doses/week) were equivalent among all treatment groups.
Three participants were withdrawn from the study for adverse events possibly related to dronabinol (dizziness and vision changes, ECG arrhythmias, headache and dizziness and vomiting)
One was withdrawn for vertigo judged probably related to dronabinol.
Subjects receiving 10 mg/day of dronabinol expressed the highest overall satisfaction with treatment (p=0.04).
In comparison to placebo, dronabinol dose-dependently reduced AHI by 10.7±4.4 (p=0.02) and 12.9±4.3 (p=0.003) events/hour at doses of 2.5 and 10 mg/day, respectively.
Average AHI in the placebo group increased over the course of the trial, whereas average AHI for both dronabinol groups decreased from baseline – albeit modestly.
Dronabinol at 10 mg/day reduced ESS score by 3.8±0.8 points from baseline (<0.0001) and by 2.3±1.2 points in comparison to placebo (p=0.05).
MWT sleep latencies, gross sleep architecture and overnight oxygenation parameters were unchanged from baseline in any treatment group.
Wrap up: 6 of 39 participants randomized to receive dronabinol were treatment ‘responders’ in contrast to 0 of 17 participants randomized to receive Placebo treatment.” Overall, the dronabinol treatment effect found in this trial was modest with considerable variation among patients. The proportion of patients with clinically meaningful improvement may be relatively small.
Note: The information on Sleep Apnea, is taken entirely and directly from their report.