Tadeh Vartanian, PharmD BCGP

The Hemp Farming Act of 2018 removed hemp, which is defined as cannabis with less than 0.3% tetrahydrocannabinol (THC), from Schedule I controlled substances and made it an ordinary agricultural commodity.

 Since then, a plethora of new research and CBD products have come on the market in a very short period of time.

For this reason, pharmacists will come across more patients who use CBD and CBD-related products, yet many pharmacists may remain uncertain of how to manage their patients’ medication regimen along with CBD.  The research and data on CBD are new and more is coming out over time, making this a dynamic medicinal agent on which to stay informed.

The Evidence Behind CBD’s Use for Sleep

The endocannabinoid system (ECS) is an extensive, endogenous signaling system with many elements that are still being discovered as research progresses. In consideration of the fact that the ECS is modulated by diet, sleep, exercise, and stress, researchers believe that the modulation of ECS may hold therapeutic promise for a diverse scope of diseases, one of which is insomnia.

demonstrated that CBD may hold promise for rapid-eye movement (REM) sleep behavior disorder, but there are mixed results and the research is still in its infancy.

In a more robust literature review of studies exploring sleep and CBD published in 

Experimental and Clinical Psychopharmacology

, the authors found that in the studies they assessed, sleep was often a secondary outcome, the study sample sizes were small, and many of the studies were short-term in nature. The authors of the review concluded that drawing any conclusions from these studies would be difficult.

A retrospective case study published in the 

 revealed that out of 72 adults who took CBD on a regular basis in a psychiatric clinic, 48 (66.7%) of them had improved sleep scores and 57 (79.2%) had reduced anxiety scores, both after the first month. The results fluctuated over time and the benefits diminished once supplementation was stopped.

This supports a larger study, published in 

, which followed 409 patients taking cannabis (not CBD) and found a 4.5-point reduction on a 0 to 10 visual analog scale of their sleep symptoms.

Overall, the data behind the use of CBD and sleep are new and in the beginning stages of development. Small studies over a short period of time do not provide conclusive evidence for the recommendation of CBD for sleep, though larger studies do seem to indicate there may be benefit for patients with insomnia. 

However, more research is needed regarding the specific ways that CBD can affect sleep, the implications of long-term use, and interactions it may have with other medications.  Finally, with CBD being a health and dietary supplement, several brands have entered the market, and so the gold standard product or brand has not yet been identified. 

At the moment, pharmacists should recommend to their patients to choose a brand of CBD that is reputable. A search on the Better Business Bureau and the FDA’s CFSAN Adverse Event Reporting System can provide information on the product’s reliability. 

Additionally, patients should be urged to take only one kind of product, to start taking it on its own so that adverse events (AEs) can be more easily identified, and to stop taking it and seek medical attention if AEs do develop, such as excessive somnolence, diarrhea, fatigue, and vomiting.

More patients may start taking or seeking CBD in their desire to achieve their optimal health. Pharmacists are the ideal health care practitioners to educate patients on these products and provide up-to-date information as it becomes available.

US Food and Drug Administration. Hemp Production and the 2018 Farm Bill. July 25, 2019. fda.gov/news-events/congressional-testimony/hemp-production-and-2018-farm-bill-07252019. Accessed October 13, 2020.

Corroon J, Felice JF. The Endocannabinoid System and its Modulation by Cannabidiol (CBD). 

. 2019: 25(S2), 6-14. pubmed.ncbi.nlm.nih.gov/31202198/.

Babson KA, Sottile J, Morabito D. Cannabis, Cannabinoids, and Sleep: a Review of the Literature. 

. 2017: 19(4), 2 doi: 10.1007/s11920-017-0775-9.

Kuhathasan N, Dufort A, MacKillop J, et al. The use of cannabinoids for sleep: A critical review on clinical trials. 

. 2019: 27(4), 383-401. doi: 10.1037/pha0000285.

Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol in Anxiety and Sleep: A Large Case Series. 

. 2019: 23, 18-41. doi: 10.7812/TPP/18-041.

Vigil JM, Stith SS, Diviant JP, et al. Effectiveness of Raw, Natural Medical Cannabis flower for Treating Insomnia under Naturalistic Conditions. 

. 2018: 5(3), 75. doi: 10.3390/medicines5030075.

Articles

A plethora of new research and CBD products have come on the market in a very short time since the Hemp Farming Act of 2018 removed hemp from Schedule I controlled substances.

CBD: Can It Help With Sleep?

Sleep is often described as one of the foundations of good health, along with diet, exercise, and relaxation. Poor sleep can cause and intensify a myriad of health disorders for nearly one-third of all Americans, according to the CDC.

Given the prevalence of poor sleep in contemporary society, it’s likely that pharmacists will come across patients with some sort of sleep disorder in their practice. One potential remedy is supplemental melatonin, which mimics the endogenous hormone that regulates our circadian rhythm.

 With OTC melatonin readily available and its product awareness high among consumers, many pharmacists may be interested in learning more about its safety and efficacy before feeling comfortable recommending it to patients who are experiencing poor sleep.

The best evidence for the use of melatonin exists for delayed sleep phase syndrome (DSPS), non-24-hour sleep wake disorder (N24), and jet lag. In the first case, a person’s sleep is delayed by 2 hours or more beyond what is considered an acceptable bedtime; for the second, a person’s biological clock fails to synchronize to a 24-hour day; and with the third, there is a mismatch between the sleep-wake cycle of the person’s internal clock to the external cues in their surroundings, often due to travel.  

For patients suffering from any of these 3 conditions, taking 0.3 mg to 5 mg melatonin can reduce the length of time needed to fall asleep and improves overall quality of life.

 Although these benefits can dissipate within a year of stopping use of the drug, it has been shown to be safe and effective if taken regularly for up to 6 years.

Specifically, in cases of jet lag, doses of 2 mg to 3 mg for those traveling eastward, when taken during the evening on the day of arrival for 2 to 5 nights, provides optimal benefit. However, studies have shown it may not be effective in decreasing the time to fall asleep or sleep efficiency, although it does improve alertness and psychomotor performance during wake time.

The evidence for insomnia, in which a person has unsatisfactory sleep despite having adequate opportunity to sleep, is modest at best. Melatonin’s effect on insomnia in the short term has been demonstrated to shorten the time needed to fall asleep by only 7 to 12 minutes with a similar 8 to 12 minute increase in total sleep quantity.

 Comorbid conditions such as depression, schizophrenia, bipolar disorder, and epilepsy tended to benefit more from supplemental melatonin for the treatment of insomnia

Finally, shift work disorder and rapid eye movement sleep behavior disorder (RBD) do not seem to respond well to melatonin. In the former condition, patients complain of insomnia and excessive sleepiness as a result of a work schedule that takes place during normal sleep periods.

Taking melatonin doesn’t seem to improve time to fall asleep, sleep efficiency, or adjustments to rotating shifts.

 In the latter condition, patients with RBD act out vivid dreams with vocal sounds and sudden movements to the point where their sleep is disturbed. Muscle paralysis with melatonin use was also noted to increase in patients with RBD, though the evidence was not as strong.

Poor sleep plagues our society in a number of ways. As front-line health care workers, pharmacists provide an easy and convenient resource for treatment and education among patients seeking to get a good night’s sleep.

Melatonin serves as an effective treatment option for those suffering from DSPS, N24, and jet lag. For insomnia, melatonin may have some potential benefit, whereas for shift-work disorder and RBD, melatonin will likely not provide much benefit. 

Overall, awareness of melatonin’s potential benefits and limitations can help pharmacists to more effectively serve patients suffering from poor sleep.

1 In 3 adults don’t get enough sleep. Centers for Disease Control and Prevention. cdc.gov/media/releases/2016/p0215-enough-sleep.html. Published February 18, 2016. Accessed August 2020.

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Nagtegaal JE, Laurant MW, Kerkhof GA, et al. Effects of melatonin on the quality of life in patients with delayed sleep phase syndrome. 

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Buscemi N, Vandermeer B, Hooton N, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. 

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Sharkey KM, Fogg LF, Eastman CI. Effects of melatonin administration on daytime sleep after simulated night shift work. 

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Wright SW, Lawrence LM, Wrenn KD, et al. Randomized clinical trial of melatonin after night-shift work: efficacy and neuropsychologic effects. 

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With OTC melatonin readily available and its product awareness high among consumers, many pharmacists may be interested in learning more about its safety and efficacy.

Melatonin and its Appropriate Use in Sleep Disorders

Medication reconciliation is among many areas in which a pharmacist’s knowledge can be used in the health care system, providing patients with appropriate care by avoiding possible medication errors and drug interactions. Medication safety is at the forefront of patient safety.

As such, pharmacist involvement in transitions of care (TOC) helps mitigate 50% of medication errors, which translates to a 28% reduction in emergency department visits, 19% drop in hospital readmissions rates, and 67% decrease in adverse drug event-related hospital revisits.

Nonprescription drugs, dietary supplements (DS), and OTC products are often overlooked by many health care providers.  The widespread use of OTC and DS are opportunities for pharmacists to not only educate patients, but also other health care members as to how these products fit into the overall health of patients.

The Consumer Healthcare Association reported that 81% of US adults use OTC medications for primary treatment of minor ailments. In addition, 93% prefer to treat their minor ailments with OTC medications before seeking professional care.

In particular, their ease of access and patients’ awareness in maintaining good health show high utilization rates for those living in rural areas or low income communities, with 83% of adults in rural areas taking at least 1 oral DS and 29% using 5 or more.

 According to consumer-products analytics firm TABS, the escalating trend of vitamins, minerals, and supplements (VMS) steadily increased from 68% in 2010 to 77% in 2019, suggesting that VMS use is here to stay and has the potential to increase over time.

Inclusion of DS and OTC products into patients’ medication profiles continue to be overlooked despite their prevalence. A study at Boston Medical Center revealed that only 60% of patients

reported the use of dietary supplements, whereas 36% had documentation of such use on their admission profile. 

Rates diminished during admission to 20% of patients reporting use due to lack of inquiry whereas only 18% disclosed DS use to a prescriber.

 Absence of documentation can contribute to missing doses of supplements a patient may be taking to maintain their health. 

Diagnoses can be missed as well, such as a patient who takes valerian root, melatonin, and chamomile on a regular basis to treat their insomnia, anxiety, or pain. Although under-reported use of DS during the admission process was demonstrated, 48% of patients intend to continue using DS after hospital discharge.

 The data suggest that medication reconciliation is vital at all stages in the process of maintaining a current and appropriate medical history.

Pharmacist-led medication reconciliation was shown to have a tremendous impact on providing identification of DS and OTC documentation. According to Karaoui et al, 71.8% of all medication histories had a discrepancy, with dietary supplements the most common agents involved (27.7%).

Nightingale et al showed an association between the use of DS/OTC products and the increased prevalence of excessive polypharmacy, defined as 4 or more unnecessary medications.

 Pharmacist involvement in each of these scenarios ensured DS and OTC products were documented and communicated to prescribers and other medical staff in a timely fashion.

TOC is the new frontier of clinical pharmacy involvement in the acute care setting.  A pharmacist’s role here is to obtain and verify the most accurate medication history of a patient and to optimize that therapy with the rest of the medical team, and nonprescription drugs are a key part of that. 

I believe the pharmacy world placed DS products specifically on the back burner in the early days of acute care treatment, but we have another opportunity to get it right now with TOC. Let us take this opportunity to perfect our medication reconciliation process and improve outcomes by asking every patient during each encounter with them about their DS and OTC use, with no exceptions. Only then can we have a complete medication history.

1. Karaoui LR et al. Impact of pharmacy-led medication reconciliation on admission to internal medicine service: experience in two tertiary care teaching hospitals. 

2. Fuji, Kevin T. The Importance of Reconciling Nonprescription Products. 

3. Shade MY et al. Analysis of Oral Dietary Supplement Use in Rural Older Adults. 

5. Gardiner P et al. Medical reconciliation of dietary supplements: Don’t ask, don’t tell. 

6. Nightingale G et al. A pharmacist-led medication assessment used to determine a more precise estimation of the prevalence of complementary and alternative medication (CAM) use among ambulatory senior adults with cancer. 

The widespread use of OTC products and dietary supplements are opportunities for pharmacists to educate patients and other health care members as to how these products fit into the overall health continuum.