It is the mixture of phytocannabinoids, terpenes and other active components present in a cannabis product that ultimately determines the therapeutic effects and side effects.Does CBD affect THC absorption and tolerance?
CBD has long been thought to influence the effects of THC. This thinking was extended to consider that CBD potentiates some of the beneficial effects of THC, as it reduces the psychoactive effects of THC and thus could improve tolerability. CBD may counteract some of the functional consequences of CB1 receptor activation in the brain.This effect has been used to explain why high CBD:THC cannabis use is less associated with the development of psychotic symptoms compared to low CBD:THC cannabis.Also, CBD is thought to interact with the cytochrome p450 enzymes that metabolize THC and thus may alter the metabolism and influence the effects of the THC consumed. It has been proposed that THC and CBD act synergistically in therapeutic use.
Yes. Methadone is known to prolong QTc intervals in up to 16% of patients.Studies have shown a linear dose response curve, with higher doses leading to a higher propensity for QTc prolongation.This has led to an FDA “black box” warning for methadone and the recommendation for routine ECG monitoring.
How have medical advances altered opioid use in cancer patients?
Cancer is no longer considered a “terminal disease.”Because of significant advances in surgical, radiation, and chemotherapeutic treatments, more than 50% of cancer patients are living greater than 2 years after the diagnosis of cancer.This allows for more cancer patients to develop chronic pain.All of these factors have led to more cancer patients taking opioids long-term.
Terpenes are aromatic components produced in the glandular part of the cannabis plant’s flower bud.Unlike cannabinoids, which are only manufactured by the cannabis plant, terpenes are manufactured by many plants and can be found in many food products, including coffee beans, ginger and cinnamon. Often, it is the terpenes that are responsible for a plant’s odor.
Similar to CB1, the CB2 receptor is a G protein receptor that serves as a target for endocannabinoids and phytocannabinoids.These CB2 receptors are primarily immunomodulatory and anti-inflammatory. They are expressed on the cell membranes of B cells, T cells and macrophages. When signaled, CB2 receptors are generally inhibitory to immune cell activation. Expression of CB2 receptors is inducible and the number of receptors is increased by inflammation.As found in studies conducted in mice, reduced CB2 receptor signaling results in increased severity of inflammation in multiple organs.
Who are the principal prescribers of opioids in the United States?
As a group, primary care physicians are the largest prescribers of opioids ( including both short-acting and long-acting opioid) in the United States. Pain physicians provide less than 6% of short-acting opioids prescriptions, but they are responsible for about 23% of extended-release opioid prescriptions. Orthopedic surgeons write for a significant percentage of short-acting opioids. A mix of other specialists is responsible for the remainder of opioid prescriptions.
The concept of cross-addiction suggests that a person addicted to one reinforcing substance is at a higher risk for addiction to other reinforcing substances. This concept is based on the fact that a person who takes an intoxicant is presumably less able to resist other temptations. The neurobiologic changes that occur with addiction appear to be common amongst most reinforcing substances. Unfortunately, there is little data to confirm the concept other than the high prevalence of polysubstance dependence.
Methadone acts as a mu opioid agonist and an NMDA antagonist. The half-life of methadone ranges from 8 to 90 hours with large inter-individual variation. Onset of analgesia occurs between 10 and 20 minutes after parenteral administration and lasts 4-5 hours. Methadone is 90% protein bound and its inactive metabolites are excreted in the urine and feces. Methadone undergoes metabolism via the cytochrome P450 system (CYP3A4, CYP2B6, and CYP2C19). Drug-drug interactions must be closely monitored.
When handing off opioid prescribing responsibilities to specialty services, what are the ethics and etiquette involved?
Communication between the prescribing physician and specialty service is paramount to a seamless transition. Unless previously coordinated, the prescribing physician should assume prescribing responsibility until the specialty service has completed a full evaluation, including urine toxicology, psychological evaluation, and a comprehensive history and physical. If the prescribing physician is uncomfortable with continued prescribing, a reasonable alternative is weaning the patient off of opioids until the specialty service has completed a full evaluation.
Do cancer patients get addicted to opioids? Do they abuse opioids?
For cancer and non-cancer patients, psychosocial factors play a contributory role in the propensity for the development of addiction and abuse. The prevalence of addiction to opioids in cancer patients varies from 0% -7.7%, while the rate of abuse ranges from 3%-5%.