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Cannabidiol prescription in clinical practice: an audit on the first 400 patients in New Zealand

Authors:
  • Te Whatu Ora

Abstract

Background: Cannabidiol (CBD) is the non-euphoriant component of cannabis. In 2017, the New Zealand Misuse of Drugs Regulations (1977) were amended, allowing doctors to prescribe CBD. Therapeutic benefit and tolerability of CBD remains unclear. Aim: To review the changes in self-reported quality of life measurements, drug tolerability, and dose-dependent relationships in patients prescribed CBD oil for various conditions at a single institution. Design & setting: An audit including all patients (n = 400) presenting to Cannabis Care, New Zealand, between 7 December 2017 and 7 December 2018 seeking CBD prescriptions METHOD: Indications for CBD use were recorded at baseline. Outcomes included EuroQol quality of life measures at baseline and after 3 weeks of use, patient-reported satisfaction, incidence of side effects, and patient-titrated dosage levels of CBD. Results: Four hundred patients were assessed for CBD and 397 received a prescription. Follow-up was completed on 253 patients (63.3%). Patients reported a mean increase of 13.6 points (P<0.001) on the EQ-VAS scale describing overall quality of health. Patients with non-cancer pain and mental-health symptoms achieved improvements to patient-reported pain and depression and anxiety symptoms (P<0.05). There were no major adverse effects. Positive side effects included improved sleep and appetite. No associations were found between CBD dose and patient-reported benefit. Conclusion: There may be analgesic and anxiolytic benefits of CBD in patients with non-cancer chronic pain and mental health conditions such as anxiety. CBD is well tolerated, making it safe to trial for non-cancer chronic pain, mental health, neurological, and cancer symptoms.
Gulbransen G etal. BJGP Open 2020; DOI: 10.3399/bjgpopen20X101010 1 of 8
RESEARCH
*For correspondence: doctor@
cannabiscare. nz
Competing interest: The authors
declare that no competing
interests exist.
Received: 12 August 2019
Accepted: 24 September 2019
Published: 05 February 2020
This article is Open Access: CC
BY license (https:// creativecom-
mons. org/ licenses/ by/4.0/)
Author Keywords: community
care, therapy in mental health,
prescribing, cannabidiol,
cannabis, anti- anxiety agents,
mental health, depression,
chronic pain, analgesics, patient
reported outcome measures
Copyright © 2020, The Authors;
DOI:10.3399/
bjgpopen20X101010
Cannabidiol prescription in clinical
practice: an audit on the first 400
patients in NewZealand
Graham Gulbransen, MBChB, FAChAM, FRNZCGP1*, William Xu2, Bruce Arroll,
MBChB, PhD, FRNZCGP3
1Private Practitioner, Cannabis Care NZ, West Care Specialist Centre, Auckland,
New Zealand; 2Medical Student, Department of General Practice and Primary Health
Care, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New
Zealand; 3Professor and Head of Department, Department of General Practice and
Primary Health Care, Faculty of Medical and Health Sciences, University of Auckland,
Auckland, New Zealand
Abstract
Background: Cannabidiol (CBD) is the non- euphoriant component of cannabis. In 2017, the New
Zealand Misuse of Drugs Regulations (1977) were amended, allowing doctors to prescribe CBD.
Therapeutic benefit and tolerability of CBD remains unclear.
Aim: To review the changes in self- reported quality of life measurements, drug tolerability, and dose-
dependent relationships in patients prescribed CBD oil for various conditions at a single institution.
Design & setting: An audit including all patients (n = 400) presenting to Cannabis Care, New Zealand,
between 7 December 2017 and 7 December 2018 seeking CBD prescriptions
Method: Indications for CBD use were recorded at baseline. Outcomes included EuroQol quality of
life measures at baseline and after 3 weeks of use, patient- reported satisfaction, incidence of side
effects, and patient- titrated dosage levels of CBD.
Results: Four hundred patients were assessed for CBD and 397 received a prescription. Follow- up was
completed on 253 patients (63.3%). Patients reported a mean increase of 13.6 points (P<0.001) on
the EQ- VAS scale describing overall quality of health. Patients with non- cancer pain and mental- health
symptoms achieved improvements to patient- reported pain and depression and anxiety symptoms
(P<0.05). There were no major adverse effects. Positive side effects included improved sleep and
appetite. No associations were found between CBD dose and patient- reported benefit.
Conclusion: There may be analgesic and anxiolytic benefits of CBD in patients with non- cancer chronic
pain and mental health conditions such as anxiety. CBD is well tolerated, making it safe to trial for non-
cancer chronic pain, mental health, neurological, and cancer symptoms.
How this fits in
CBD prescription in primary care was legalised in New Zealand in 2017. Previous preclinical trials
have shown CBD to have anxiolytic and anti- inflammatory properties but there remains a paucity
of studies investigating its therapeutic potential. In this quantitative observational study of the first
400 patients prescribed CBD in New Zealand, CBD was well tolerated amongst patients with a wide
range of conditions and symptoms. Quality- of- life benefit was experienced to a greater degree in
patients living with non- cancer chronic pain and anxiety- related mental- health conditions, and to a
lesser degree in patients with cancer or neurological symptoms.
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Introduction
With the amendment of the New Zealand Misuse of Drugs Regulations 1977 in 2017, CBD has
become a legal prescription medicine. The amendment recognises the right of New Zealand doctors
to prescribe CBD products that contain no more of 2% of 9-Δ-tetrahydrocannabinol (9-Δ-THC) in the
product.1
CBD and 9-Δ-THC are cannabinoids, active compounds found within the Cannabis genus of
plants.2 While 9-Δ-THC is the main psychoactive component responsible for euphoria and the ‘high’
associated with marijuana, CBD is the non- euphoriant component.2,3
CBD is currently FDA- approved for the treatment of Dravet and Lennox- Gastaut syndrome, two
childhood seizure disorders.4 Randomised controlled trials (RCTs) have shown that, when CBD is added
to existing anti- epileptic medication in patients with these syndromes, seizure frequency decreases.5,6
However, CBD shows potential therapeutic use beyond this. Pre- clinical studies demonstrate that
CBD has potential anti- inflammatory effects via inhibition of immune cell migration, which may be
useful in chronic inflammatory conditions.7
Moreover, preclinical studies have demonstrated anxiolytic effects of CBD.3,8–10 Crippa et al found
that in patients with generalised anxiety disorder given 400 mg of oral CBD, there was decreased
cerebral blood flow to anxiety processing areas of the brain and a decrease in patient- reported
anxiety when compared to placebo.8 CBD in one double- blinded placebo- controlled RCT decreased
symptoms of social anxiety disorder patients and fear of public speaking.10 CBD may also reduce
psychotic symptoms of schizophrenia.11
CBD appears to be safe for patients, with a recent phase I dosage trial showing purified CBD oil
is well tolerated up to doses of 6000 mg.12 However, due to a paucity of clinical studies, prescribing
guidelines are lacking.
The aim of this study was to conduct a clinical audit on the patient population referred to Cannabis
Care (a primary care clinic in Auckland, New Zealand) for CBD oil. The authors explored the indications
for prescribing CBD oil, patient quality of life, patient satisfaction, and self- titrated dosage levels.
Method
The STROBE statement for reporting observational studies was followed.13
Patients
Patients included in this audit were those who were prescribed CBD from 7 December 2017 to 7
December 2018. Patients included in this audit either were referred by their primary care provider
or self- referred to the service. Patients were prescribed CBD oil (Tilray CBD100, Tilray, Nanaimo, BC,
Canada) containing 100 mg CBD/mL in 25 mL bottles administered orally via a dropper. Bottles costed
approximately USD300 each, which was self- funded as CBD is not on the New Zealand government-
subsidised pharmaceutical schedule (PHARMAC).
Outcomes
Patient sex, age, and details of medical condition were recorded at first consultation. Each participant
was grouped into one of four broad clinical groups based on their presenting medical symptoms: non-
cancer chronic pain symptoms, neurological symptoms, mental health- related symptoms, or cancer
symptoms. When a patient presented with symptoms fitting multiple categories, the clinician assigned
the patient to the category fitting their primary presenting complaint.
Patients completed an EQ- 5D- 5L questionnaire at baseline before taking CBD, and again after at
least 3 weeks of using the medicine as part of routine clinical assessment. The EQ- 5D- 5L is a two- part
tool consisting of the EQ- 5D- 5L descriptive system and the EQ Visual Analogue scale (EQ- VAS).14
The descriptive system measures five domains (mobility, self- care, usual activities, pain or discomfort,
anxiety or depression) each with five levels of severity: no problems, slight problems, moderate
problems, severe problems, and extreme problems. The EQ- VAS is a 20 cm vertical printed scale from
0 to 100 whereby the upper endpoint of the scale corresponds the ‘best health you can imagine’ and
the lower corresponds to the ‘worst health you can imagine’. The patient rated their current overall
health on this visual scale to yield a corresponding numerical score.
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Patients also rated their satisfaction with their CBD use at follow- up. They rated their experience
as ‘no benefit, good, very good, or excellent’ and reported any side effects. In addition, variations
in patient dosage and the duration and frequency of CBD oil intake were recorded where possible.
Statistical methods
The EQ- 5D- 5L data was measured on ordinal scales and hence considered as non- parametric data.
The EQ- VAS scores were recorded on a continuous scale and treated as a parametric variable. Non-
parametric data was presented as median (interquartile range [IQR]) and analysed for differences
using the Wilcoxon rank sum test. Change in patient EQ- VAS scores was presented as mean (standard
deviation [SD]) and analysed using one- way analysis of variance (ANOVA) to assess any differences
between indication categories. Binary logistic regression was used to analyse potential dose-
dependent responses, dose of CBD, and patient- reported benefit.
Categorical data such as the indications for CBD, patient satisfaction with CBD use, and side effects
of use were presented as frequencies. A P value of ≤0.05 was taken as statistically significant. SPSS
software (version 23.0) was used for statistical analysis.
Results
A total of 400 patients presented to Cannabis Care from 7 December 2017 to 7 December 2018.
Three patients did not receive a prescription based on a clinician decision that they would not benefit.
Patients receiving CBD prescription consisted of 214 females (53.9%) and 183 males (46.1%), for a
total of 397 individuals. The mean age of patients was 51.48 years (SD 19.1). Of those prescribed CBD,
61 patients (15.4%) fit more than one category of indication and were assigned to a group based on
their primary condition.
Patient indication for CBD prescription is shown in Table1. The non- cancer pain symptoms group
included patients with fibromyalgia, osteoarthritis, rheumatoid arthritis, neuropathic pain, chronic non-
specific pain, pain due to ulcerative colitis, and migraines. Cancer- related symptoms included pain,
nausea, poor appetite, emotional distress, and adverse effects of radiotherapy and/or chemotherapy
treatment. Mental health symptoms included anxiety disorders, depressive disorders, post- traumatic
stress disorder, and insomnia. Neurological symptoms included Parkinson’s disease, multiple sclerosis,
epilepsy, autism spectrum disorder with challenging behaviour, amyotrophic lateral sclerosis, multiple
system atrophy, various neuropathies, and tremors.
Of the 397 patients initially prescribed the CBD oil, 253 (63.7%) were followed up either through
a second appointment with the clinician or by phone. In total, 250 patients (63.0%) reported their
satisfaction with CBD use, with three patients (0.8%) refusing to comment. Within these 250 patients,
a subset of 110 patients (27.7%) completed before and after EQ- 5D- 5L questionnaires; 144 patients
(36.3%) did not complete follow- up assessment, with 82 patients (20.7%) lost to follow- up and 62
patients (15.6%) choosing not to take the CBD. Reasons for patients not taking the CBD included
death, financial barriers preventing purchase of the oil, severe illness, participation in a clinical trial, or
consumption of alternative illicit cannabis products.
Median follow up duration for patients who completed their CBD prescription was 36 days (IQR
28–65).
Table 1 Baseline characteristics
Characteristic Frequency, nProportion, %
Mean age, years (±SD) 51.48 (±19.1)
Sex Male 183 46.1
Female 214 53.9
Indication for CBD prescription Non- cancer pain symptoms 181 45.6
Mental health symptoms 64 16.1
Neurological symptoms 60 15.1
Cancer symptoms 92 23.2
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Outcomes of CBD treatment
Results from Wilcoxon rank sum tests for EQ- 5D- 5L domains found that patients experiencing non-
cancer pain symptoms had a significant improvement of self- reported mobility scores (P = 0.02), ability
to complete their usual activities (P = 0.007), self- reported pain (P<0.001), and self- reported anxiety
or depression (P = 0.017). Patients with mental- health related symptoms experienced improvements
to their ability to carry out their usual activities (P = 0.002), pain (P = 0.039), and anxiety or depression
(P = 0.02). Patients with neurological symptoms experienced no statistically significant differences
in any of the five domains. Patients with cancer symptoms experienced improvements in pain (P =
0.047). Complete results of EQ- 5D- 5L questionnaires are shown in Table2.
Treatment with the CBD in all population groups showed an increase in the EQ- VAS score. There
was an overall mean increase of EQ- VAS score of 13.6 points (P<0.001, 95% CI = 9.72 to 16.76).
Overall, EQ- VAS scores represented an improvement in self- reported health. Results of one- way
ANOVA tests showed that there were no significant differences between indication groups for the
improvement of EQ- VAS scores.
Patient- reported satisfaction of CBD treatment found that 175 patients (70.0% of the 250 patients
for whom there was available data, or 44.1% of the 397 patients prescribed the CBD), reported some
level of satisfaction with CBD use (good, very good, or excellent). Seventy- five patients (30.0% of
250 patients, or 19.0% of 397 patients) reported no benefit from CBD use. There was no statistically
significant relationship found between patient age or sex and patient- reported satisfaction.
Table 2 Baseline and follow- up EQ- 5D- 5L
Indication for CBD
prescription
Domain of
EQ- 5D- 5L
Baseline EQ- 5D-
5L scores, median
(IQR)
Follow- up EQ- 5D- 5L
scores, median (IQR) P value
Non- cancer pain
symptoms
(n = 53)
Mobility 2.0 (1.0 to 3.0) 2.0 (1.0 to 3.0) 0.022
Self- care 1.0 (1.0 to 2.0) 1.0 (1.0 to 2.0) 0.046
Usual activities 3.0 (2.0 to 4.0) 2.0 (1.0 to 3.0) 0.007
Pain/discomfort 3.5 (3.0 to 4.0) 3.0 (2.0 to 3.0) <0.001
Anxiety/depression 2.0 (1.0 to 3.0) 2.0 (1.0 to 2.0) 0.017
Mental health
symptoms
(n = 21)
Mobility 1.0 (1.0 to 1.0) 1.0 (1.0 to 1.0) 0.577
Self- care 1.0 (1.0 to 1.75) 1.0 (1.0 to 1.0) 0.096
Usual activities 3.0 (2.0 to 3.0) 1.0 (1.0 to 2.0) 0.002
Pain/discomfort 2.0 (1.0 to 3.0) 1.0 (1.0 to 2.0) 0.039
Anxiety/depression 4.0 (3.0 to 4.0) 2.0 (1.5 to 3.0) 0.002
Neurological symptoms
(n = 11)
Mobility 1.0 (1.0 to 3.0) 1.5 (1.0 to 2.0) 0.317
Self- care 1.0 (1.0 to 3.0) 1.5 (1.0 to 2.0) 0.317
Usual activities 3.0 (1.75 to 4.0) 2.5 (1.75 to 3.25) 0.194
Pain/discomfort 3.0 (1.5 to 3.5) 3.0 (1.5 to 3.0) 0.18
Anxiety/depression 3.0 (2.0 to 3.0) 1.5 (1.0 to 3.0) 0.194
Cancer symptoms
(n = 24)Mobility 1.0 (1.0 to 2.0) 1.0 (1.0 to 2.0) 0.56
Self- care 1.0 (1.0 to 2.0) 1.0 (1.0 to 1.0) 1
Usual activities 2.0 (1.0 to 2.75) 2.0 (1.0 to 3.0) 1
Pain/discomfort 3.0 (2.0 to 3.0) 2.0 (1.0 to 2.5) 0.047
Anxiety/depression 2.0 (1.0 to 3.0) 1.0 (1.0 to 2.0) 0.11
Score of 1 = no problems, 2 = slight problems, 3= moderate problems, 4 = severe problems, 5 = extreme
problems. P values are calculated from Wilcoxon rank sum tests. ‘Before’ scores taken at rst consultation. ‘After’
scores taken after at least 3 weeks of cannabidiol intake.
CBD = cannabidiol. IQR = interquartile range.
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Side effects
Adverse effects such as sedation and vivid dreams were experienced by 25 out of 253 patients
(9.9%). A worsening of a pre- existing condition was reported by 2 of 253 (0.8%) patients upon follow-
up. Thirty- eight of followed- up patients (15.0%) reported positive side effects of CBD use, such as
improved sleep or improved appetite. Side effects experienced by follow- up patients are summarised
in Table3.
Dosage
Amongst those who completed the course of CBD, the dose per day ranged from 40mg/day to
300mg/day. However, dosage information was incomplete, existing for only 110 patients out of the
253 followed- up patients (43.5%). The clinician recommended dosing to at least 100 mg/day. Overall
dosage between patients varied widely and was reported inconsistently by patients. Binary logistic
regression analysis was conducted for the existing values and there was no significant association
between dosage and patient- reported benefit from CBD (P = 0.145).
Discussion
Summary
CBD treatment improved self- reported quality of life measures for patients in the non- cancer pain and
mental health- related symptom groups. There was no statistically significant improvement in those
with cancer or neurological symptoms. Of those prescribed CBD, 44.1% (or 70.0% of the follow-
up group) reported good to excellent benefit for relatively intractable conditions; 19.0% of those
prescribed CBD (or 30.0% of the follow- up group) reported no benefit. CBD is well tolerated in most
patients and may be of benefit to patients with various intractable chronic conditions.
Strengths and limitations
The strength of this study is that it assesses effects of CBD on a large range of chronic medical
conditions in a clinical context. Only three patients were excluded (due to extreme severity of their
conditions).
Table 3 Side effect profile of the followed- up patients (n = 253)
Side effect Frequency, n (%)
Positive effects
Improved sleep 31 (12.3)
Improved appetite 7 (2.8)
Adverse effects
Sedation 5 (2.0)
Vivid dreams 5 (2.0)
Emotional disturbances eg, irritable,
depressed, anxious
5 (2.0)
Disorientation 3 (1.2)
Sleeplessness 1 (0.4)
Nausea 1 (0.4)
Constipation 1 (0.4)
Diarrhoea 1 (0.4)
Headaches 1 (0.4)
Oral mucosa irritation 1 (0.4)
Hallucinations 1 (0.4)
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There are several limitations to this present audit. There was a large loss to follow- up due to patients
not attending follow- up and cost barriers. Hence, the results reported may not be fully representative
of the entire patient population. Moreover, patients had to pay USD300 for 2500 mg of the CBD oil,
USD150 for an initial consultation, and USD75 for follow- up. Most patients had refractory chronic pain
and conditions resistant to conventional treatment uncommon in the wider population, increasing
risk of selection bias. These patients are unlikely to be representative of a wider, more generalised
cohort of patients. It is difficult to elucidate the effect of selection bias on these findings. The high cost
barriers may augment the placebo effect of treatment,15 resulting in an overestimation of treatment
effects. However, due to many patients having resistant symptoms, CBD may conversely prove more
efficacious in patients with less severe symptoms.
The follow- up period was variable, resulting in interviews with some patients who had stopped
taking CBD for a period of months. This may have confounded the patient’s recollection of the
effects of CBD, likely causing an underestimation of the effect. Some follow- up was completed by the
clinician instead of a non- clinical author. This increased the risk of expectation bias by the clinician,
likely overestimating the effect. Considering these limitations, results should be interpreted with the
appropriate caution.
Comparison with existing literature
Numerous preclinical trials9,10 and neuro- imaging studies8 have demonstrated the anxiolytic effects of
CBD. A recently published case- series in psychiatric patients found a benefit of CBD for anxiety and
sleep,16 which is in agreement with the above findings.
On a pharmacological level, preclinical trials suggest CBD’s analgesic action is due to its effect on
certain receptors: TRPV1 and a3 GlyRs, involved in nociceptive transmission. However, human studies
are still inconclusive.17–19 The apparent benefit of CBD on pain reported by patients in this audit
remains difficult to interpret. Current guidelines for the prescription of medicinal cannabis, including
both 9-Δ-THC and CBD, recommend it as a third- line treatment for ‘neuropathic pain, palliative and
end- of- life pain, chemotherapy- induced nausea and vomiting, and spasticity due to multiple sclerosis
or spinal cord injury’.20 However, RCTs investigating the use of CBD alone for the treatment of pain
are lacking.
The ineffectiveness of the CBD oil for 75 of the 250 patients with available data (30.0%) may be
due to lack of patient compliance and inadequate dosing. The expense of the pure CBD 100 mg/
mL may have influenced patient attitudes towards this matter. Previous studies investigating CBD’s
anxiolytic effect have shown a U- shaped dose curve with highest efficacy at 300 mg as a single- dose.21
This audit did not find a statistically significant dose- response, likely due to missing data and the
aforementioned factors regarding financial cost.
CBD’s ineffectiveness in improving self- reported health in patients in the cancer and neurological
groups may be due to the high heterogeneity of the clinical presentations within these groups.
Additionally, patients within these groups had more severe disease progression compared to the
mental health and non- cancer pain symptom groups, which may have limited efficacy.
Overall, CBD treatment was well tolerated with mild adverse effects, most commonly related to
sedation. This is consistent with the findings of a phase I clinical trial showing the main side effects
of CBD were related to the gastrointestinal and central nervous system.12 Patient- reported sleep
benefits are likely related to these sedative effects. While cannabis (containing both 9-Δ-THC and
CBD) has been indicated for use as an appetite stimulant in HIV- affected patients with cachexia,22,23 it
remains unclear if CBD alone has significant appetite stimulating effects beyond placebo. Long- term
side effects were not analysed in this current audit and future study is still needed to clarify chronic
effects of CBD administration.24
Implications for research and practice
Some urgency on this topic exists due to the increasing worldwide legalisation of cannabis and its
related products. A focus should be placed on confirming the anxiolytic effects of CBD in clinical
conditions. Future studies should investigate the effectiveness of full spectrum CBD oil with the
retention of terpenes, the essential oils found in cannabis plants. Terpenes may enhance the effects of
pure CBD because of a synergistic effect known as the entourage effect.
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Overall, this audit demonstrated the potential benefit of CBD in treating anxiety and pain. The
present study shows that it improves quality of life for a diverse range of patients. CBD in this
population has been shown to be safe and well tolerated. However, despite potential biases of
patients influenced by the high treatment cost, pure CBD is not effective for all. Benefit was more
pronounced in patients who had conditions with less severe disease progression (such as mental
health or non- cancer chronic pain conditions). Due to lack of a control group, high drop- out rate, and
an extreme patient population, these study results should be interpreted with caution. Future studies
should investigate effects of long- term CBD use, which could not be analysed in this present audit.
Funding
This research was not funded.
Ethical approval
The NZ National Health and Disability Ethics Committee does not require ethics approval for audit
data.
Provenance
Freely submitted; externally peer reviewed.
Acknowledgements
The authors would like to acknowledge and thank Associate Professor Stephen Buetow for assis-
tance in proofing the manuscript and Bert van der Werf for statistical guidance.
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... Several other small studies, single case studies, and case series reported improvements in anxiety at lower doses (25-300 mg, 0.4-4.3 mg/kg bw/day) [210][211][212][213], and there are multiple other clinical trials on anxiety currently ongoing [214]. Of the various effects studied with CBD, anxiety relief at doses of 300-400 mg (4.3-5.7 mg/kg bw/day) has emerged as the most reproducible result [193]. ...
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Background: Cannabidiol (CBD) is a cannabinoid present in the hemp plant (Cannabis sativa L.). Non-medicinal CBD oils with typically 5–40% CBD are advertised for various alleged positive health effects. While such foodstuffs containing cannabinoids are covered by the Novel Food Regulation in the European Union (EU), none of these products have yet been authorized. Nevertheless, they continue to be available on the European market. Methods: The Permanent Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) reviewed the currently available data on adverse and potential beneficial effects of CBD in the dose range relevant for foods. Results: Increased liver enzyme activities were observed in healthy volunteers following administration of 4.3 mg CBD/kg bw/day and higher for 3–4 weeks. As lower doses were not tested, a no observed adverse effect level (NOAEL) could not be derived, and the dose of 4.3 mg/kg bw/day was identified as the lowest observed adverse effect level (LOAEL). Based on the CBD content and dose recommendations of CBD products on the market, the SKLM considered several exposure scenarios and concluded that the LOAEL for liver toxicity may be easily reached, e.g., via consumption of 30 drops of an oil containing 20% CBD, or even exceeded. A critical evaluation of the available data on potential beneficial health effects of CBD in the dose range at or below the LOAEL of 4.3 mg/kg bw/day revealed no scientific evidence that would substantiate health claims, e.g., in relation to physical performance, the cardiovascular, immune, and nervous system, anxiety, relaxation, stress, sleep, pain, or menstrual health. Conclusions: The SKLM concluded that consumption of CBD-containing foods/food supplements may not provide substantiated health benefits and may even pose a health risk to consumers.
... Previous literature supports our findings on the effects of THC for acute pain relief (Hill, 2015;Whiting et al., 2015b). However, there is limited research suggesting that CBD also has acute analgesic effects (Gulbransen et al., 2020;Palmieri et al., 2017), which was not found in the present study. Continued research, particularly on recreational and medically accessible cannabis products, is greatly needed to improve our understanding of the effectiveness of these products and their cannabinoid profiles for pain relief. ...
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Introduction Cannabis, commonly known for both therapeutic and intoxicating effects, is gaining accessibility on legal markets and traction as a potential alternative therapy for pain mediation, particularly in those suffering from chronic low back pain. However, the effectiveness in this population of legal market forms of cannabis, particularly commonly used edibles, is unknown. Methods Therefore, this study utilized a naturalistic prospective design where participants with chronic low back pain with intentions to initiate cannabis use for treatment were recruited and self-selected edible cannabis products containing varying amounts of delta- 9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Products were categorized as CBD-dominant, THC-dominant, or combined THC and CBD (THC + CBD). Results 249 participants [140 female (56.62%), mean (SD) age of 46.30 (16.02), 90% White] were tracked over 2 weeks of ad libitum use and assessed during a naturalistic acute cannabis administration session on changes in pain, mood, and subjective drug effects. During acute administration, a significant correlation between THC dose and short-term pain relief was found, suggesting that higher THC doses were associated with greater pain reduction (p < .05). In addition, THC was associated with higher levels of subjective cannabis drug effects (p < .001), regardless of whether CBD was also in the edible product. Acute CBD dose was primarily associated with short-term tension relief (p < .05); however, there were no associations between CBD dose and acute pain. Over the 2-week ad libitum administration period results suggested pain reductions across participants using all forms of cannabis. However, trends suggested that more frequent use of CBD-dominant edible cannabis may be associated with greater reductions in perceived pain over the 2-week observation period (p = .07). Discussion These findings support the short-term analgesic effects of THC and anxiolytic effects of CBD and further suggest that orally-administered THC and CBD should continue to be evaluated for the potential to provide both acute and extended relief from chronic low back pain. Clinical Trial Registration https://clinicaltrials.gov/study/NCT03522324?locStr=Boulder,%20CO&country=United%20States&state=Colorado&city=Boulder&cond=chronic%20low%20back%20pain&intr=Cannabis&rank=1, identifier NCT03522324.
... Cannabidiol (CBD) is one of the many cannabinoids found in the Cannabis sativa plant. It has diverse and multiple molecular targets [18] and anti-inflammatory, anxiolytic, anticonvulsant and antipsychotic properties [18][19][20][21][22][23][24]. Importantly in the context of CUD, CBD is a negative allosteric modulator of the activity of cannabinoid type 1 receptors within the central nervous system, restricting the ability of THC to bind to these receptors, thus reducing THC action [25]. ...
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Background Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. Methods/Design A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. Discussion Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1–6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. Trial registration Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).
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Background An innovative New South Wales government funded statewide Cannabis Medicines Advisory Service (CMAS) operated between January 2018 and June 2022. The service provided comprehensive patient‐specific and evidence‐based information to support health professionals in prescribing and patient care decisions. This study aimed to describe real‐world data collected by CMAS. Methods A sub‐set of de‐identified, patient‐specific enquiries collected between January 2021 and June 2022 (n = 123/567; 21.7%) were analyzed using R version 4.2.1. Diagnosis, indication, and comorbidities were coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology. Results Most patient‐specific enquiries from medical practitioners were from general practitioners (n = 103/123; 83.7%). Female (n = 53/123; 43.1%) and male (n = 59/123; 48.0%) patients were similarly represented. Sex was not specified for 8.9% (n = 11/123) of patients. The mean age of patients was 52.1 years (range <10–90). The most common three diagnoses were osteoarthritis, anxiety, and chronic pain. Indications that were most frequently reported included chronic pain, anxiety, back pain, non‐neuropathic pain, and insomnia. Comedications were most commonly non‐opioid and opioid analgesics and antidepressants. Most practitioners were considering prescribing a cannabidiol (CBD) product for their patient. Cannabinoid composition selection guidance provided by CMAS was predominantly (delta‐9‐tetrahydrocannabinol) THC:CBD ~1:1, followed by CBD‐only products. CMAS was contacted by health professionals regarding the management of potential adverse events for five patients. Conclusion The findings of this study shed light on the information medical practitioners were seeking to inform their clinical decision‐making about medical cannabis and can inform the development of clinical guidance resources.
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Cannabis is widely used medicinally, both as a prescribed medicine and as a form of self-medication. While it is relatively easy to define what cannabis is (it is a plant of a specific species), it is unclear what is meant by “medical cannabis.” In this paragraph, we propose that instead of speaking of medical cannabis as a type of substance, it is more useful to focus on what types of cannabis use count as medical, that is, what are the conditions for the use of cannabis to be considered as medical. We argue that the term “medical cannabis” cannot be restricted just to certified and clinically controlled cannabis products, given that most cannabis variants that are used medically are not certified in this way. Moreover, it is implausible to define medical cannabis as cannabis prescribed by a clinician, as the policies for prescription vary widely across countries. Rather, in assessing whether cannabis use counts as medical, we argue that we should consider its benefit-risk ratio both on the population level as well as in a given individual. On this approach, cannabis use can be considered as medical if its medical or therapeutic effects outweigh possible negative ones. However, population-level data is highly limited in several indications, and the research suffers from complexities, such as great variation in cannabis products that are used, as well as problems in controlling for the placebo effect due to the psychoactive effects of certain types of cannabis. From population-level data one cannot directly infer whether a medicine is effective in an individual, due to individual differences. Thus, in assessing whether the use of cannabis by a patient counts as medical, we should assess its effects on him or her. But how to rule out on the individual level that the perceived beneficial effects are not due to a mere placebo effect, which could be boosted by the psychoactive, subjectively felt effects of cannabis? We argue that the psychoactive effects of cannabis could be part of its therapeutic mechanism, instead of side effects that should be eliminated. This renders the notion of placebo problematic, as has been argued in the case of classical psychedelics. We conclude that the self-perceived therapeutic efficacy of cannabis is an important factor in considering whether the use is medical, in addition to scientific evidence of efficacy.
Article
Background Since medical access to medicinal cannabis (MC) was legalised in Australia in 2016, numbers of people prescribed MC have increased exponentially. There is a need for safety and effectiveness data on the longer-term use of MC in real-world settings. This paper describes the methodology of Project Twenty21 Australia, an observational study that commenced early in 2022 and its preliminary findings. Method This study tests whether medicinal cannabis is effective in four primary conditions: chronic pain, anxiety, posttraumatic stress disorder and multiple sclerosis (MS). Participants are prescribed MC from within a Project Formulary, completing questionnaires at baseline then 3 monthly for up to 12 months. Results Between the start of the study in February and 30 August 2022, 278 participants had been recruited into the study: 50.7% female, 48.2% male and 1.1% non-binary with average age 39.2 years (18–77). Patients reported a low quality of life and high levels of co-morbidity. Three-month data, available for 71 participants, indicate that MC was associated with substantial improvements in self-reported quality of life, general health, mood/depression and sleep with standardised effect size estimates ranging from 0.57 to 0.93. Three adverse reactions were reported. Conclusions This paper describes the protocol used for an observational study conducted in Australia assessing the effectiveness of MC in four main conditions. We have established the feasibility of collecting real-world data on symptoms and quality of life in people receiving treatment with MC. Preliminary evidence suggests that MC may be effective in improving quality of life, general health, mood and sleep.
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Context: Cannabidiol (CBD) is one of many cannabinoid compounds found in cannabis. It does not appear to alter consciousness or trigger a "high." A recent surge in scientific publications has found preclinical and clinical evidence documenting value for CBD in some neuropsychiatric disorders, including epilepsy, anxiety, and schizophrenia. Evidence points toward a calming effect for CBD in the central nervous system. Interest in CBD as a treatment of a wide range of disorders has exploded, yet few clinical studies of CBD exist in the psychiatric literature. Objective: To determine whether CBD helps improve sleep and/or anxiety in a clinical population. Design: A large retrospective case series at a psychiatric clinic involving clinical application of CBD for anxiety and sleep complaints as an adjunct to usual treatment. The retrospective chart review included monthly documentation of anxiety and sleep quality in 103 adult patients. Main outcome measures: Sleep and anxiety scores, using validated instruments, at baseline and after CBD treatment. Results: The final sample consisted of 72 adults presenting with primary concerns of anxiety (n = 47) or poor sleep (n = 25). Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%) but fluctuated over time. In this chart review, CBD was well tolerated in all but 3 patients. Conclusion: Cannabidiol may hold benefit for anxiety-related disorders. Controlled clinical studies are needed.
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Background A formal single ascending and multiple dose pharmacokinetic (PK) trial of cannabidiol (CBD) oral solution was required to determine the safety and tolerability of CBD, the maximum tolerated dose, and to examine the effect of food on CBD PK parameters. Objective This trial assessed the safety, tolerability and PK of CBD oral solution in healthy adult volunteers, as well as the effect of food on CBD PK parameters. Methods The study consisted of three arms: single ascending dose (1500, 3000, 4500 or 6000 mg CBD [n = 6 per group]/placebo [n = 8; 2 per CBD dose group]), multiple dose (750 or 1500 mg CBD [n = 9 per group]/placebo [n = 6; 3 per CBD dose group] twice daily), and food effect (1500 mg CBD single dose [n = 12]). All subjects completed all trial arms and were analyzed as planned. Results CBD was generally well tolerated. Diarrhea, nausea, headache, and somnolence were the most common adverse events (AEs) across all trial arms, with an increased incidence of some gastrointestinal and nervous system disorder AEs (most notably diarrhea and headache) apparent in subjects taking CBD compared with placebo. All AEs were of mild or moderate severity; none were severe or serious. There were no deaths or discontinuations in the trial. After single oral doses, CBD appeared rapidly in plasma; time to maximum plasma concentration (tmax) was approximately 4–5 h. The major circulating metabolite was 7-carboxy-CBD, then parent CBD, 7-hydroxy-CBD (active metabolite), and 6-hydroxy-CBD (a relatively minor metabolite). Plasma exposure to CBD [maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to time t (AUCt)] increased in a less than dose-proportional manner (Cmax slope 0.73; AUCt slope 0.64). Oral clearance of CBD was high (1111–1909 L/h) and apparent volume of distribution was large (20,963–42,849 L). CBD reached steady state after approximately 2 days, with moderate accumulation (1.8- to 2.6-fold) after 750 and 1500 mg CBD twice daily. After 7 days, a twofold increase in CBD dose resulted in 1.6- and 1.9-fold increases in geometric mean Cmax and area under the plasma concentration-time curve over a dosing interval (AUCτ), respectively. CBD elimination was multiphasic; the terminal elimination half-life was approximately 60 h after 750 and 1500 mg CBD twice daily; and effective half-life estimates ranged from 10 to 17 h. Cmax was 541.2 ng/mL and AUCτ was 3236 ng·h/mL after 1500 mg CBD twice daily. A high-fat meal increased CBD plasma exposure (Cmax and AUCt) by 4.85- and 4.2-fold, respectively; there was no effect of food on tmax or terminal half-life. Conclusion CBD was generally well tolerated. Most AEs were mild in severity; none were severe or serious. The safety and PK profile support twice-daily administration of CBD.
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Clinical studies indicate that cannabidiol (CBD), the primary non-addictive component of cannabis that interacts with the serotonin (5-HT) 1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact in models of neuropathic pain are unknown. First, using in-vivo single unit extracellular recordings in rats, we demonstrated that acute intravenous (i.v.) increasing doses of CBD (0.1-1.0 mg/kg) decreased the firing rate of 5-HT neurons in the dorsal raphe nucleus (DRN), which was prevented by administration of the 5-HT1A antagonist WAY 100635 (0.3 mg/kg, i.v.) and the TRPV1 antagonist capsazepine (1 mg/kg, i.v.) but not by the CB1 receptor antagonist AM 251 (1 mg/kg, i.v.). Repeated treatment with CBD (5 mg/kg/day, subcutaneously, s.c, for 7 days) increased 5-HT firing via desensitization of 5-HT1A receptors. Rats subjected to the spared nerve injury (SNI) model for 24 days showed decreased 5-HT firing activity, mechanical allodynia, and increased anxiety-like behavior in the elevated plus maze (EPMT), open field (OFT), and novelty suppressed feeding tests (NSFT). Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Anti-allodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), while the anxiolytic effect was blocked only by WAY. Overall, repeated treatment with low-dose CBD induces analgesia predominantly via TRPV1 activation, reduces anxiety via 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
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Objective: To develop a clinical practice guideline for a simplified approach to medical cannabinoid use in primary care; the focus was on primary care application, with a strong emphasis on best available evidence and a promotion of shared, informed decision making. Methods: The Evidence Review Group performed a detailed systematic review of 4 clinical areas with the best evidence around cannabinoids: pain, nausea and vomiting, spasticity, and adverse events. Nine health professionals (2 generalist family physicians, 2 pain management-focused family physicians, 1 inner-city family physician, 1 neurologist, 1 oncologist, 1 nurse practitioner, and 1 pharmacist) and a patient representative comprised the Prescribing Guideline Committee (PGC), along with 2 nonvoting members (pharmacist project managers). Member selection was based on profession, practice setting, location, and lack of financial conflicts of interest. The guideline process was iterative through content distribution, evidence review, and telephone and online meetings. The PGC directed the Evidence Review Group to address and provide evidence for additional questions as needed. The key recommendations were derived through consensus of the PGC. The guideline was drafted, refined, and distributed to a group of clinicians and patients for feedback, then refined again and finalized by the PGC. Recommendations: Recommendations include limiting medical cannabinoid use in general, but also outline potential restricted use in a small subset of medical conditions for which there is some evidence (neuropathic pain, palliative and end-of-life pain, chemotherapy-induced nausea and vomiting, and spasticity due to multiple sclerosis or spinal cord injury). Other important considerations regarding prescribing are reviewed in detail, and content is offered to support shared, informed decision making. Conclusion: This simplified medical cannabinoid prescribing guideline provides practical recommendations for the use of medical cannabinoids in primary care. All recommendations are intended to assist with, not dictate, decision making in conjunction with patients.
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Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September, 2004, with methodologists, researchers, and journal editors to draft a che-cklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed explanation and elaboration document is published separately and is freely available on the websites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE statement will contribute to improving the quality of reporting of observational studies.
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The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD) in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg), and CBD (100, 300, and 900 mg). The subjects were underwent a test of public speaking in a real situation (TPSRS) where each subject had to speak in front of a group formed by the remaining participants. Each subject completed the anxiety and sedation factors of the Visual Analog Mood Scale and had their blood pressure and heart rate recorded. These measures were obtained in five experimental sessions with 12 volunteers each. Each session had four steps at the following times (minutes) after administration of the drug/placebo, as time 0: -5 (baseline), 80 (pre-test), 153 (speech), and 216 (post-speech). Repeated-measures analyses of variance showed that the TPSRS increased the subjective measures of anxiety, heart rate, and blood pressure. Student-Newman-Keuls test comparisons among the groups in each phase showed significant attenuation in anxiety scores relative to the placebo group in the group treated with clonazepam during the speech phase, and in the clonazepam and CBD 300 mg groups in the post-speech phase. Clonazepam was more sedative than CBD 300 and 900 mg and induced a smaller increase in systolic and diastolic blood pressure than CBD 300 mg. The results confirmed that the acute administration of CBD induced anxiolytic effects with a dose-dependent inverted U-shaped curve in healthy subjects, since the subjective anxiety measures were reduced with CBD 300 mg, but not with CBD 100 and 900 mg, in the post-speech phase.
Article
Background Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox–Gastaut syndrome, a severe developmental epileptic encephalopathy. Methods In this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox–Gastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks. The primary outcome was the percentage change from baseline in the frequency of drop seizures (average per 28 days) during the treatment period. Results A total of 225 patients were enrolled; 76 patients were assigned to the 20-mg cannabidiol group, 73 to the 10-mg cannabidiol group, and 76 to the placebo group. During the 28-day baseline period, the median number of drop seizures was 85 in all trial groups combined. The median percent reduction from baseline in drop-seizure frequency during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg cannabidiol group, and 17.2% in the placebo group (P=0.005 for the 20-mg cannabidiol group vs. placebo group, and P=0.002 for the 10-mg cannabidiol group vs. placebo group). The most common adverse events among the patients in the cannabidiol groups were somnolence, decreased appetite, and diarrhea; these events occurred more frequently in the higher-dose group. Six patients in the 20-mg cannabidiol group and 1 patient in the 10-mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial. Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations. Conclusions Among children and adults with the Lennox–Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adverse events with cannabidiol included elevated liver aminotransferase concentrations. (Funded by GW Pharmaceuticals; GWPCARE3 ClinicalTrials.gov number, NCT02224560.)
Article
Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs. Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients' compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam's side effects. Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.
Article
Background The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome. Methods In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period. Results The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, −22.8 percentage points; 95% confidence interval [CI], −41.1 to −5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient’s overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group. Conclusions Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375.)
Article
The high and increasing prevalence of medical marijuana consumption in the general population invites the need for quality evidence regarding its safety and efficacy. Herein, we synthesize extant literature pertaining to the phytocannabinoid cannabidiol (CBD) and its brain effects. The principle phytocannabinoid Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and CBD are the major pharmacologically active cannabinoids. The effect of CBD on brain systems as well as on phenomenological measures (e.g. cognitive function) are distinct and in many cases opposite to that of Δ⁹-THC. Cannabidiol is without euphoriant properties, and exerts antipsychotic, anxiolytic, anti-seizure, as well as anti-inflammatory properties. It is essential to parcellate phytocannabinoids into their constituent moieties as the most abundant cannabinoid have differential effects on physiologic systems in psychopathology measures. Disparate findings and reports related to effects of cannabis consumption reflect differential relative concentration of Δ⁹-THC and CBD. Existing literature, notwithstanding its deficiencies, provides empirical support for the hypothesis that CBD may exert beneficial effects on brain effector systems/substrates subserving domain-based phenomenology. Interventional studies with purified CBD are warranted with a call to target-engagement proof-of-principle studies using the research domain criteria (RDoC) framework.