July 2019

The fentanyl transdermal patch has a slow onset and long duration of action. Therapeutic blood levels are achieved 12-16 hours after application of a patch and the half-life is 16-22 hours after removal of the patch. A fentanyl patch, therefore, would not effectively treat breakthrough pain.

Fentanyl is metabolized via the cytochrome P450 (CYP) 3A4 system. Extreme caution must be taken when administering fentanyl, if the patient is on other medications that inhibit the CYP3A4 system.

Patients who are not opioid tolerant are at risk for developing severe hypoventilation, when given fentanyl for breakthrough pain.

Breakthrough pain occurs in 33-65% of patients with chronic cancer pain.

Cannabinoids, such as dronabinol as well as non-pharmaceutical preparations, are commonly used by HIV and AIDS patients in an attempt to counter nausea caused by antiretroviral therapy. A single study among 88 individuals used a visual analogue scale to measure changes in nausea and found that nausea was reduced by 22% among those randomly assigned to dronabinol (2.5mg TID), compared to 7% in those assigned a placebo (p<0.05).

There is no “gold standard” opioid tapering schedule. The tapering schedule should be modified to address the patient’s needs and overall health, and is dependent on the specific opioid being tapered. Short-acting opioid tapering schedules differ from the long-acting tapering schedules. Furthermore, there are specific recommendations for each of the long-acting opioids. For example, the recommendations for a methadone taper differ from that of a morphine taper.

The effect of cannabinoids on HD patients may be unique compared to other populations, as HD is characterized by widespread dysfunction in the ECS. Analyses of human tissue have consistently found that CB1 receptor levels and ligand binding decline by 50% in the caudate and putamen, and 25% in the cortex, in early symptomatic HD patients that have presented with chorea for 1 year. Levels of CB2 receptors and FAAH are higher, while levels of N-acyl phosphatidylethanolamine-specific phospholipase D are lower in putamen tissue from late-stage HD patients. Thus, cannabinoid therapy is highly likely to differentially effect HD patients compared to other populations. Importantly, cannabinoid therapies may have different effects depending on the stage of HD and specific symptom presentation.

Yes. There are defects in the endocannabinoid system in persons with epilepsy. In one study, 12 patients with newly diagnosed temporal lobe epilepsy had lower levels (p < .01) of anandamide in CSF as compared to controls. In tissue removed from 30 patients undergoing epilepsy surgery, the levels of CB1 receptor messenger RNA were lower in some excitatory nerve endings as compared to the specimens obtained post mortem from persons without epilepsy. It was also noted that in the epilepsy patients, there was reduced expression of diacylglycerol lipase, the enzyme that synthesizes 2-AG in postsynaptic neurons.

In animal models, cannabinoids have been shown to be synergistic with opioids in reducing pain. A small pharmacokinetic interaction study of vaporized cannabis (900mg of 3.56% THC herbal cannabis with no CBD), administered once on days 1 and 5, and t.i.d on days 2 – 4 in 21 chronic pain patients on sustained release morphine (10) or oxycodone (11) showed no significant effect on opioid plasma concentrations when cannabis was added but did suggest increased analgesia. A RCT of nabiximols in 359 cancer patients with poorly controlled pain despite a stable opioid regimen found that the sublingual preparation at 4 sprays (10.8 mg THC and 10 mg THC), 10 sprays (27 mg THC and 25 mg CBD) or 16 sprays (43.2 mg THC and 40 mg CBD) daily for 5 weeks decreased pain and sleep disruption.

Rimonabant, a cannabinoid medicine that selectively blocks CB1 receptors, was approved in the European market as an anti-obesity drug in 2006. It was withdrawn in 2009 due to potential serious adverse events, including depression, anxiety, and suicidal ideation. The U.S. Food and Drug Administration had never approved Rimonabant, due to the increased risk of psychiatric events.