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Reduction of Benzodiazepine Use in Patients Prescribed Medical Cannabis 1 Dalhousie Medical School Class of 2019, Dalhousie University Faculty of Medicine, Undergraduate Medical Education, My experience using CBD for anxiety, with reviews of Sunday Scaries CBD gummies, Grön CBD chocolate, and Beekeeper's Naturals B.Chill Honey.

Reduction of Benzodiazepine Use in Patients Prescribed Medical Cannabis

1 Dalhousie Medical School Class of 2019, Dalhousie University Faculty of Medicine, Undergraduate Medical Education, Halifax, Canada.

Andrew Davis

2 Department of Economics, Acadia University, Wolfville, Canada.

Nico Moolman

3 Division of Otolaryngology—Head and Neck Surgery, Department of Surgery, Dalhousie University, Halifax, Canada.

S. Mark Taylor

3 Division of Otolaryngology—Head and Neck Surgery, Department of Surgery, Dalhousie University, Halifax, Canada.

1 Dalhousie Medical School Class of 2019, Dalhousie University Faculty of Medicine, Undergraduate Medical Education, Halifax, Canada.

3 Division of Otolaryngology—Head and Neck Surgery, Department of Surgery, Dalhousie University, Halifax, Canada.

* Address correspondence to: Chad Purcell, BScH, BSc(Pharm), Dalhousie Medical School Class of 2019, Dalhousie University Faculty of Medicine, Undergraduate Medical Education, 5820 University Avenue, 3rd Floor Dickson Building, Halifax B3H 4R2, Canada, [email protected]

This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Benzodiazepines are a class of medication with sedative properties, commonly used for anxiety and other neurological conditions. These medications are associated with several well-known adverse effects. This observational study aims to investigate the reduction of benzodiazepine use in patients using prescribed medical cannabis.

Methods: A retrospective analysis was performed on a cohort of 146 medical cannabis patients (average age 47 years, 61% female, 54% reporting prior use of cannabis) who reported benzodiazepine use at initiation of cannabis therapy. These data are a part of a database gathered by a medical cannabis clinic (Canabo Medical). Descriptive statistics were used to quantify associations of the proportion of benzodiazepine use with time on medical cannabis therapy.

Results: After completing an average 2-month prescription course of medical cannabis, 30.1% of patients had discontinued benzodiazepines. At a follow-up after two prescriptions, 65 total patients (44.5%) had discontinued benzodiazepines. At the final follow-up period after three medical cannabis prescription courses, 66 total patients (45.2%) had discontinued benzodiazepine use, showing a stable cessation rate over an average of 6 months.

Conclusion: Within a cohort of 146 patients initiated on medical cannabis therapy, 45.2% patients successfully discontinued their pre-existing benzodiazepine therapy. This observation merits further investigation into the risks and benefits of the therapeutic use of medical cannabis and its role relating to benzodiazepine use.

Introduction

Benzodiazepines are a class of medications commonly used to treat a variety of neurological conditions. 1 Hypnotic and anxiolytic properties make benzodiazepines a mainstay in the treatment of insomnia and anxiety disorders, as well as alcohol, seizure, and spasticity disorders. These effects are exerted by amplification of inhibitory neural signaling, primarily via gamma-aminobutyric acid receptors. 2 A comprehensive review of the pharmacologic properties of benzodiazepines is outside the scope of this study, but can be found elsewhere. 3

Annual incidence rates of benzodiazepine use vary across North American populations and regions, with estimates upward of 10%. 4,5 Likewise, Canadian survey data suggest benzodiazepine use has consistently been within the range of 5% in 2003 to 10% in 2012. 6 Benzodiazepines are considered to have a relatively good safety profile in comparison with older sedative hypnotics, such as barbiturates. However, common side effects include ataxia, dizziness, drowsiness, fatigue, slowed reaction, and muscle weakness. 1 Complications of long-term use include lack of concentration, dependence, tolerance, overdose, and addiction. 2 A recent meta-analysis found increased mortality in benzodiazepine users compared with nonusers, with a hazard ratio (HR) of 1.6 (p≤0.05). 7 This has similarly been shown in a systematic review demonstrating an increase in overall mortality in regular benzodiazepine users, with a HR ranging from 1.2 to 1.7 in the studies reviewed. 8 While benzodiazepines remain an essential class of medication, there is certainly need for caution regarding its side effect profile.

This study seeks to investigate benzodiazepine discontinuation rates in a population of patients referred for medical cannabis therapy.

Materials and Methods

A retrospective analysis was performed on a cohort of patients using medical cannabis. These data are part of an ongoing database gathered by Canabo Medical Clinic on medical cannabis patients. At the time of this study, there were 10 clinics operating in Ontario, Alberta, Nova Scotia, and Newfoundland, accepting patients exclusively through referral. Canabo clinics comprised physicians who specialize in the controlled prescribing of medical cannabis for a variety of medical conditions, to whom other health care providers can refer patients. All patients in the study were referred to Canabo by practicing physicians outside the clinic network. Deidentified patient data were obtained in collaboration with Canabo Medical and the electronic health records provider, InputHealth.

Canabo physicians collect self-reported patient information at each clinic visit. Three follow-up appointments were considered adequate to ensure sufficient collection of patient-reported information. Physicians typically wrote prescriptions for 2-month periods, with an average period between visits of 61.3 days, although exact times varied with patient schedules and physician discretion. Based on average prescription durations, patients could reach three follow-up visits in just over 6 months. Due to variability in prescribing practices and adherence, patients enrolled within 9 months of the study end date could be included. The study end date was October 31, 2016, and patients were eligible for inclusion if their first visit to Canabo was before January 31, 2016. Canabo records identified 884 patients who were using benzodiazepines at the time of their initial visit to the clinic, before prescription of cannabis. Six hundred seventy-seven patients were excluded because sufficient information could not be collected before the study end date. Of the 207 patients who initiated cannabis before January 31, 2016, 146 (70.5%) completed three follow-up visits and formed the study sample. No patients were excluded for any other reason, including past medical cannabis usage, indication for medical cannabis or benzodiazepines, previous discontinuation, or any observable characteristics. To evaluate patient’s perceived burden of disease, they were asked “how often is your life affected/impacted by your medical condition,” and given options to answer were as follows: “all the time,” “most of the time,” and “occasionally/rarely” ( Table 2 ).

Table 2.

Self-Reported Impact of Medical Condition on Quality of Life by All Patients at Initial Visit to Canabo Clinic, and by Benzodiazepine Use Status After Three Visits

Impact on life First visit—all patients After three visits—BD use After three visits—no BD use
How often is your life affected/impacted by your medical condition All the time 74.0% 45.0% 30.3%
Most of the time 22.6% 38.8% 43.9%
Occasionally/rarely 3.4% 16.3% 25.8%
Chi-square >0.1

Benzodiazepine management and discontinuation was not a specific goal of any Canabo physician, and benzodiazepine cessation may have been initiated by a physician or patients. Patients were not tested for verification of reported benzodiazepine discontinuation. Referring physicians were sent consultation and follow-up notes regarding their respective patient’s progress under medical cannabis treatment.

Statistical testing via binomial t-tests was used to assess population mean differences in benzodiazepine use after each clinic visit, following initiation of medical cannabis therapy. Approaches involving estimating regression models were deemed unsuitable, given sample size limitations. The potential relevance of the Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content of cannabis used, and differences in the patients’ perceived impact of their medical condition(s) on their life were evaluated using chi-square tests.

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Results

Sample demographics did not identify any significant discrepancies between patients who discontinued their benzodiazepines and those who did not. The mean age of participants was 47.7 years with a standard deviation of 12.7 years. Prior use of cannabis was self-reported by 54% of patients. A total of 97.6% of patients were not currently using other recreational drugs and 73.3% had never used recreational drugs that were not cannabis. Concurrent alcohol and cigarette use was reported in 41.4% and 30.8% of patients, respectively. Results on the discontinuation of benzodiazepine use by each of these groups are presented in Table 1 .

Table 1.

Sample Demographics and Outcomes

Mean Final BD use Final no BD use Significance of difference
Age (years) 47.7 47.2 48.3 NS (p>0.1)
Female 61.0% 61.3% 60.6% NS (p>0.1)
Using cannabis at intake 54.3% 50.3% 59.1% NS (p>0.1)
No current recreational drug use 97.6% 98.1% 97.0% NS (p>0.1)
No history of non-cannabis recreational drug use 73.0% 73.1% 72.7% NS (p>0.1)
Current alcohol use 41.4% 41.9% 40.9% NS (p>0.1)
Current cigarette use 30.8% 32.5% 28.8% NS (p>0.1)
Chronic condition (>3 years) 80.1% 80.9% 80.0% NS (p>0.1)

BD, benzodiazepine; NS, not significant.

Reported primary conditions driving cannabinoid treatment were grouped into neurological (7.5%), pain (47.9%), psychiatric conditions (31.9%), and other (12.7%). Small sample sizes prevent a strong assessment of the link between medical condition and benzodiazepine use.

After the first visit, 44 patients (30.1%) had discontinued their benzodiazepines. Another 21 patients, for a total of 65 patients (44.5%), had discontinued their benzodiazepines by the second visit. By the third visit, one more patient had discontinued benzodiazepines, for a total of 66 patients (45.2%) The reduction between the initial visit and first follow-up is significant at the p

Percent decline in benzodiazepine use among patients at follow-up time points after initiating medical cannabis treatment.

On their initial visit, 74% of patients reported that their “life is affected/impacted by [my] medical condition” “all the time.” After three clinic visits, 45.0% of patients using benzodiazepines, and 30.3% of patients who discontinued benzodiazepines reported that their life was impacted by their medical condition “all the time” ( Table 2 ; chi-square >0.1).

The distribution of cannabinoid (CBD and THC) proportions was not significantly different among patients who continued and those who discontinued benzodiazepines ( Table 3 ; chi-square >0.1).

Table 3.

Δ9-Tetrahydrocannabinol and Cannabidiol Content of Cannabis Used by a Sample Population by Benzodiazepine Use Status

Mean Final BD use Final no BD use
THC level
>20% 20.2% 14.7% 26.8%
15–19.9% 34.7% 36.8% 32.1%
10–14.9% 12.1% 16.2% 7.1%
5–9.9% 13.7% 14.7% 12.5%
1–4.9% 7.3% 7.4% 7.2%
4.0% 2.9% 5.4%
Unknown 8.1% 7.4% 8.9%
Chi-square >0.1
CBD level
>17% 7.3% 5.9% 8.9%
12–16.9%% 13.7% 14.7% 12.5%
8–11.9% 18.6% 14.7% 23.2%
4–7.9% 13.7% 16.2% 10.7%
1–3.9% 8.1% 11.8% 3.6%
17.8% 14.7% 21.4%
Unknown 21.0% 22.1% 19.7%
Chi-square >0.1

CBD, cannabidiol; THC, Δ9-tetrahydrocannabinol.

Discussion

Patients initiated on medical cannabis therapy showed significant benzodiazepine discontinuation rates after their first follow-up visit to their medical cannabis prescriber, and continued to show significant discontinuation rates thereafter. Discontinuation was not associated with any measured demographic characteristic. Patients also reported decreased daily distress due to their medical condition(s) following prescription cannabinoids. The CBD and THC content of cannabis used did not differ among patients who continued and those who discontinued benzodiazepines.

The observed association between medical cannabis use and benzodiazepine discontinuation should not be misinterpreted as causative, and these results do not support inferences about substitution of medical cannabis for benzodiazepine therapy. Substitution of cannabis for opioids is supported by a growing body of evidence, although many challenges and unknowns limit widespread adoption of cannabis use for this indication. 9,10 Extrapolation of self-reported data suggests that there are potentially as many Canadians using cannabis for its sedative and anxiolytic properties as there are patients taking sedatives such as benzodiazepines. 11,12 The substitution effect of medical cannabis has also been seen with medications for pain, anxiety, migraine, depression, chronic pain, and headache. 10,13,14

This study found no significant difference in the proportions of CBD and THC in the cannabis used by patients who continued and those who discontinued benzodiazepines. This study did not intend to address the relationship between cannabis and anxiety, or the physiological mechanisms of THC and CBD. However, review of the literature on this topic is warranted, as the effects of cannabis on anxiety are not fully understood. 15 Animal studies have reported anxiolytic effects of whole cannabis administration. 16 Experimental animal evidence cannot be easily generalized to human consumption because the use of dried cannabis flower may exhibit varying effects. These effects may be dependent on factors such as proportions and interactions among cannabinoids, amount used, and method of use. The potency of cannabis has been increasing over the past two decades. THC content has been increasing and CBD content decreasing, resulting in an increase in THC:CBD ratios from 14:1 in 1995 to 80:1 in 2014. 17 Previous studies have reported associations of high THC/low CBD content with increased risk of anxiety. 18 CBD and THC have proposed conflicting effects on anxiety. CBD has been associated with anxiolytic effects regardless of dose, while THC reliably produces subjective effects of anxiety, but appears to be anxiolytic at lower doses and anxiogenic at higher doses. 15,19 Pre-clinical studies of CBD have demonstrated promise in treating anxiety disorders. 20 Animal models support a reduction of anxiety symptoms in relation to generalized anxiety disorder and post-traumatic stress disorder through CBD treatment. 21,22 Human and animal studies suggest that CBD may have role in attenuating the effects of THC, including anxiety. 15 The observed association of benzodiazepine discontinuation with use of medical cannabis highlights the importance of further characterization of the anxiolytic properties of cannabis in the future.

Medical cannabis use has increased dramatically in recent years. The total number of Canadians registered for medical cannabis as of September 30th increased from 12,409 in 2014, to 30,537 in 2015 and 98,460 in 2016. 23 Canabo clinics experienced similar growth from 2014 through 2015 with patient volumes expanding by more than double each year. Canabo data accessed in October 2016 consisted primarily of new patients from the same calendar year. Of the 207 patients who initiated medical cannabis with Canabo by January 31, 2016, 61 patients did not complete three visits before study end date. The designation of a 9-month window to receive three follow-up visits may contribute to these lost 61 patients. These patients may have received prescriptions for >3 months, or used their medical cannabis less frequently than discussed with their physician. Patient reasons for discontinuing clinic treatment are unknown and may include the typical reasons for loss to follow-up from any medical clinic.

There are several limitations to the current study. This study is not designed to, nor should be used to hypothesize physiological mechanisms to explain this observed association between benzodiazepines and cannabis. The retrospective observational methodology and sample size preclude an inference of a causal relationship between cannabis and benzodiazepine use trends. Sample size limitations also preclude our ability to make inference from the smaller proportion of benzodiazepine discontinuers than continuers who reported that their medical condition affected their life all the time after three clinic visits. Without dependable safety data and evidence from randomized trials for this cohort, cannabis cannot be recommended as an alternative to benzodiazepine therapy. Retrospective analysis of pre-existing Canabo data from ongoing clinic standard operating procedures precludes examination of many potentially valuable parameters for study, such as benzodiazepine dosing, indication and duration of use, and information about patients’ intentions with discontinuation. No objective measure of benzodiazepine discontinuation was used to confirm self-reported data. Future studies could make use of biomarkers to more closely characterize benzodiazepine discontinuation. Although relative proportions of THC and CBD were reported, data did not include the strain of cannabis, or method of use. Consistent use of cannabis was approximated by patients returning to clinic three times after initial visit. Consistent use was thereby inferred from patients consistently returning to clinic. The present study demonstrates an association between medical cannabis therapy and reductions in benzodiazepine use. There is a fundamental paucity of research on the effectiveness of cannabis as a medical therapy, as well as the risks and benefits of its use. 24 Future studies should aim to expand on the current understanding of cannabis and its potential medical applications.

Conclusion

Medical cannabis remains a controversial but potentially effective treatment for patients suffering from a variety of medical conditions. Within a cohort of patients initiated on medical cannabis therapy, a large proportion successfully discontinued their pre-existing benzodiazepine therapy. This study therefore supports the continued research of medical cannabis and urges further exploration into its therapeutic value.

Acknowledgments

No sources of funding were obtained for completion of this study. No grants or stipends were received by any authors for their work in completing this study. The Acadia University Research Ethics Board declined to engage in full review, deeming the research exempt from review mandates, as per article 2.4 of the Canadian Tri-Council Policy Statement on Ethical Conduct for Research Involving Humans.

Abbreviations Used

CBD cannabidiol
HR hazard ratio
THC Δ9-tetrahydrocannabinol

Author Disclosure Statement

A.D. has an ongoing financial relationship with Canabo Medical, in which Canabo Medical financially compensates A.D. for private corporate data analysis services of patient prescriptions for strictly commercial purposes. This arrangement has no impact on the academic data analyses of this anonymized data set and is therefore unrelated to the present study. We acknowledge this as a potential competing interest. C.P., N.M., and S.M.T.: No competing financial interests exist.

Cite this article as: Purcell C, Davis A, Moolman N, Taylor SM (2019) Reduction of benzodiazepine use in patients prescribed medical cannabis, Cannabis and Cannabinoid Research 4:3, 214–218, DOI: 10.1089/can.2018.0020.

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I Swapped My Xanax for CBD. Here’s What Happened.

Anxiety has been part of my life for so long that I don’t really know who I am without it. I have obsessive-compulsive disorder and also just a high-strung, anxious nature. When things are going well, I tend to take a glass-half-full perspective and link my drive and work ethic to the ever-present anxiety that pushes me to always do more. But when things are going badly, sometimes it’s hard to function like a normal person because I’m so paralyzed with fear.

For those times, I’ve been prescribed Xanax. And it helps, for sure. But the thing is, I get nervous about taking it. (Yes, that’s right—I get anxious about taking the medication that’s supposed to make me less anxious. I am a disaster, y’all.)

Even at the smallest doses, it makes me sleepy, so I don’t like to take it during the day. And although nighttime is usually when my anxiety peaks, even then, I don’t want to take it often because I’m afraid of becoming dependent.

CBD for anxiety—does it work?

A mom friend who, like me, suffers from OCD, mentioned she was taking CBD for anxiety. My interest was piqued based on her experience—when her anxiety felt particularly out-of-control, the CBD would put a stop to the spiraling.

I asked my doctor about it, and she was dubious. While she gave the approval for me to give it a try, she cautioned that because marijuana is illegal, CBD hasn’t been researched enough to determine its impact on anxiety.

While this is true, the research that has been done on CBD (short for cannabidiol) looks promising [ source ]. There’s a growing body of evidence demonstrating CBD’s usefulness for treating anxiety-related disorders [ source ]. It seems to have a calming effect on the central nervous system [ source ], which gives it the potential to treat a multitude of disorders.

In 2018, the FDA unanimously recommended approval for an epilepsy drug made from CBD called Epidiolex [ source ], and it is now the first CBD medicine available in the U.S. [ source ]. Because of its FDA approval, it is now regulated and does not have any of the safety concerns that other forms of CBD carry. A few studies have been carried out that show inaccuracies in the labeling of CBD products sold online [ source ] and from retail outlets [ source ], revealing large ranges of variability in the product contained.

It took me a while to actually take the plunge and try CBD for anxiety because I had trouble finding sources that felt trustworthy. (As someone who quite literally obsesses over product purity—it’s one of my OCD fixations—this is the best argument I can think of to legalize marijuana. Legalization means regulation and research [ source ]!)

What helped me was:

  • Actually reaching out to the manufacturers to ask questions . This was huge for me. If you have a good BS meter, I’d recommend taking this step. The folks at Grön were especially candid and helpful. I learned so much from them!
  • Getting recommendations . I asked friends, the staff at my local grocery co-op, and checked Reddit and internet message boards. Plus, I Google everything!
  • Treating CBD like other health supplements . I always buy supplements that share third-party testing results on their websites, are transparent about their sourcing, and manufacture their products in the United States or Canada. The CBD industry is not regulated, and thus the safety and efficacy of products on the market are not guaranteed, so you need to do your homework [ source ].

Just to be clear, CBD doesn’t get you high. The compound that gives you that feeling when you use marijuana is called THC . And if you feel high after taking CBD, you’re probably taking a product that’s impure or mixed with other elements for that purpose [ source ].

My Experience Taking CBD for Anxiety

Before I talk about my experience using CBD for anxiety, you may be wondering, “Is CBD even legal?!” Well, yes, it is—kind of. What’s not legal in some places is CBD derived from marijuana, unless you’re in a state where marijuana is legal [ source ].

But, if you want to get off that bandwagon altogether, you can look into CBD derived from hemp and other sources. Grön , a CBD chocolate maker out of Portland, produces its CBD from an invasive pine tree and lemon peel. This kind of CBD is not illegal.

The first CBD product I tried was Beekeeper’s Naturals B. Chill honey . This felt like a natural place to start since it was a brand I already knew and trusted. The effect was hard to describe; it wasn’t so much any particular feeling, but the absence of the ever-present anxiety that’s just always there for me.

I tend to carry tension in my body, and I’m never still. I drive everyone around me crazy by constantly fidgeting and bouncing my legs. The CBD made my body feel calm and quiet.

That quiet feeling was mental too. My need to multitask and inability to concentrate on anything for longer than 5 minutes gave way to intense focus. I worried that CBD, like Xanax, would render me useless, but I’ve actually found that taking CBD helps me with work. Unlike the Xanax, which I’d always have to time around bedtime, I feel comfortable taking CBD any time of the day.

Could it be a placebo effect? It very well could be. I don’t know! All I know is that CBD seems as effective for me as my prescription. And I haven’t had to take any Xanax since I started using CBD. I have two unfilled prescriptions sitting in my purse right now and a half-used bottle in the medicine cabinet.

I soon picked up a few bars of Grön CBD chocolate (found after some intense Googling) and Sunday Scaries gummies after the owner reached out to Hello Glow via Instagram. Now I have a stockpile ready for any time of day: honey for stirring into morning tea, a bottle of gummies to go with me in my purse, and chocolate to have after dinner to help me sleep better.

That said, I’m not taking CBD all day long, or even every day. Unfortunately, CBD is pricey, so I use it in the same way I used my Xanax—only when I really need it. When I’m having a particularly bad day with anxiety, it’s usually the result of my mind latching onto some random thought and not letting go. The CBD helps me let those thoughts pass through rather than allowing them to snowball into something paralyzing.

It feels a little strange—even kind of scary—to be talking about this because CBD isn’t yet mainstream. And while slathering it on your skin is one thing, actually ingesting it is another.

But we’re currently undergoing a sea change in how we talk about mental illness in this country; if we can be open about that, we should also be open about treatment options. CBD has a stigma attached to it because of its origins, but the fact that it’s a non-addictive alternative to benzodiazepines and opiates makes it worth researching and taking seriously. It’s not just for potheads.

Of course, all the usual disclaimers apply here. I’m not a doctor! If CBD is something you’re considering, talk to your doctor! And, obviously, my experience is my own. What worked for me might not be right for you. Just make sure and do the research, so you will feel comfortable with whatever you decide to do.

This post was medically reviewed by Dr. Susanna Quasem, M.D., a child, adolescent, and adult psychiatrist in Nashville, Tennessee. Learn more about Hello Glow’s medical reviewers here . As always, this is not personal medical advice, and we recommend that you talk with your doctor.

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