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Plasma concentrations of Δ 9-tetrahydrocannabinol (THC), its metabolite 11-hydroxy-THC (11-OH-THC), and cannabidiol (CBD) after inhalation of 3 cannabis varieties, Bedrocan (A), Bediol (B), and Bedrolite (C). Data are mean 6 95% confidence interval.

Plasma concentrations of Δ 9-tetrahydrocannabinol (THC), its metabolite 11-hydroxy-THC (11-OH-THC), and cannabidiol (CBD) after inhalation of 3 cannabis varieties, Bedrocan (A), Bediol (B), and Bedrolite (C). Data are mean 6 95% confidence interval.

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In this experimental randomized placebo-controlled 4-way crossover trial, we explored the analgesic effects of inhaled pharmaceutical-grade cannabis in 20 chronic pain patients with fibromyalgia. We tested 4 different cannabis varieties with exact knowledge on their [INCREMENT]-tetrahydrocannabinol (THC) and cannabidiol (CBD) content: Bedrocan (22....

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Context 1
... inhalation of all 3 active treatments, THC, its metabolite 11-OH-THC, and CBD, were detectable with the following CMAX and TMAX values (Fig. 2). Bedrocan: THC 82 6 20 ng/mL at t 5 5 minutes, 11-OH-THC 5 6 3 ng/mL at 10 minutes, and CBD 0.2 6 0.3 ng/mL at 5 minutes; Bediol: THC 76 6 35 ng/mL at t 5 5 minutes, 11-OH-THC 5 6 3 ng/mL at 10 minutes, and CBD 80 6 029 ng/mL at 5 minutes; and Bedrolite: THC 13 6 5 ng/mL at t 5 5 minutes, 11-OH-THC 0.9 6 0.5 ng/mL at 10 minutes, and ...
Context 2
... pharmacokinetic analysis showed that peak THC con- centrations were similar after Bedrocan and Bediol inhalation, whereas the peak THC concentration after Bedrolite inhalation was about one-sixth of that of the other 2 varieties (Fig. 2). These are important observations and indicate that magnitude of THC plasma concentrations was partly dependent on the presence of CBD in the inhalant. In Bedrocan, 24-mg inhaled THC (and ,1-mg CBD) produced a mean THC peak plasma concentration of 82 ng/mL. In the other 2 cannabis varieties with CBD contents of about 18 mg, THC plasma ...
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... a possible CBD- induced increase in pulmonary THC uptake, for example, due to an increase in pulmonary blood flow. We are unaware of any data that support this mechanism; (2) CBD-induced inhibition of THC metabolism. Although CBD potently inhibits THC metabolism in the rat, 14 our data do not support any inhibition of THC conversion to 11-OH-THC (Fig. 2); and (3) cyclizing of CBD into THC. Because both compounds are chemically related, CBD can convert into THC; this has been observed after subcutaneous administration of CBD in the rat. 14 To further improve our understanding of the pharmacokinetic behavior of THC under different CBD conditions, we plan a compartmental pharmacokinetic ...
Context 4
... inhalation of all 3 active treatments, THC, its metabolite 11-OH-THC, and CBD, were detectable with the following CMAX and TMAX values (Fig. 2). Bedrocan: THC 82 6 20 ng/mL at t 5 5 minutes, 11-OH-THC 5 6 3 ng/mL at 10 minutes, and CBD 0.2 6 0.3 ng/mL at 5 minutes; Bediol: THC 76 6 35 ng/mL at t 5 5 minutes, 11-OH-THC 5 6 3 ng/mL at 10 minutes, and CBD 80 6 029 ng/mL at 5 minutes; and Bedrolite: THC 13 6 5 ng/mL at t 5 5 minutes, 11-OH-THC 0.9 6 0.5 ng/mL at 10 minutes, and ...
Context 5
... pharmacokinetic analysis showed that peak THC concentrations were similar after Bedrocan and Bediol inhalation, whereas the peak THC concentration after Bedrolite inhalation was about one-sixth of that of the other 2 varieties (Fig. 2). These are important observations and indicate that magnitude of THC plasma concentrations was partly dependent on the presence of CBD in the inhalant. In Bedrocan, 24-mg inhaled THC (and ,1-mg CBD) produced a mean THC peak plasma concentration of 82 ng/mL. In the other 2 cannabis varieties with CBD contents of about 18 mg, THC plasma ...
Context 6
... a possible CBDinduced increase in pulmonary THC uptake, for example, due to an increase in pulmonary blood flow. We are unaware of any data that support this mechanism; (2) CBD-induced inhibition of THC metabolism. Although CBD potently inhibits THC metabolism in the rat, 14 our data do not support any inhibition of THC conversion to 11-OH-THC (Fig. 2); and (3) cyclizing of CBD into THC. Because both compounds are chemically related, CBD can convert into THC; this has been observed after subcutaneous administration of CBD in the rat. 14 To further improve our understanding of the pharmacokinetic behavior of THC under different CBD conditions, we plan a compartmental pharmacokinetic ...

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... Fibromyalgia One clinical trial investigated CBD among people with fibromyalgia. Inhaled cannabis with varying concentrations of THC and CBD was administered to 20 women with fibromyalgia to assess pain responses [28]. Following a single inhalation of three cannabis products (22% THC, ˂1% CBD; 6.3% THC, 8% CBD; 9% CBD, ˂ 1% THC; and placebo without THC or CBD), none of the active treatments had an effect that was greater than placebo on spontaneous pain or electrical pain response. ...
... CBD is a substrate for CYP2C19 and CYP3A4 with potential to increase serum concentrations of antidepressants, tofacitinib, and reduce concentrations of clopidogrel. Inhaled CBD can boost serum THC concentration, potentially resulting in increased psychoactive effects [28]. In a recent study of CBD administered to 120 frontline healthcare professionals who experienced burnout related to COVID-19, adverse events of increased liver function tests were observed in 4 of the 59 subjects receiving CBD 150 mg twice daily over a period of 28 days [53]. ...
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Purpose of Review This review will address the many uncertainties surrounding the medical use of cannabidiol (CBD). We will begin with an overview of the legal and commercial environment, examine recent preclinical and clinical evidence on CBD, explore questions concerning CBD raised by healthcare professionals and patients, investigate dosing regimens and methods of administration, and address current challenges in the accumulation of sound evidence. Recent Findings CBD has potential for relief of symptoms of pain, sleep, and mood disturbance in rheumatology patients, but sound clinical evidence is lacking. CBD is safe when accessed from a regulated source, whereas wellness products are less reliable regarding content and contaminants. Dosing for symptom relief has not yet been established. Summary As many rheumatology patients are trying CBD as a self-management strategy, the healthcare community must urgently accrue sound evidence for effect.
... Notably though, THC has shown promising analgesic efficacy (Abrams et al., 2007;Ellis et al., 2009;Ware et al., 2010;Wilsey et al., 2013;Wallace et al., 2015;Wilsey et al., 2016;van de Donk et al., 2019). This analgesic effect of THC is still under investigation but likely mirrors THC's concentration and thus cannabis' intoxication potential (Wilsey et al., 2013;Andreae et al., 2015;Wallace et al., 2015;van de Donk et al., 2019). ...
... Notably though, THC has shown promising analgesic efficacy (Abrams et al., 2007;Ellis et al., 2009;Ware et al., 2010;Wilsey et al., 2013;Wallace et al., 2015;Wilsey et al., 2016;van de Donk et al., 2019). This analgesic effect of THC is still under investigation but likely mirrors THC's concentration and thus cannabis' intoxication potential (Wilsey et al., 2013;Andreae et al., 2015;Wallace et al., 2015;van de Donk et al., 2019). In clinical trials studying the analgesic efficacy for cannabis, the THC concentrations utilized are consistently <10% (Abrams et al., 2007;Ellis et al., 2009;Ware et al., 2010;Wilsey et al., 2013;Wallace et al., 2015;Wilsey et al., 2016). ...
... Literature suggests that different concentrations of THC and CBD and different ratios of THC:CBD induce variances in experienced subjective effects (Pennypacker and Romero-Sandoval, 2020). In fact, it appears that certain lower ratios of THC:CBD are more apt to produce an attenuation of THC induced effects (Dalton et al., 1976;Englund et al., 2013;van de Donk et al., 2019) while higher ratios are more likely to enhance THC induced effects (Arkell et al., 2019;Solowij et al., 2019;van de Donk et al., 2019). For instance, one study found that inhaled cannabis at a 2:1 THC:CBD ratio (8 mg THC (1.6%)/4 mg CBD (0.8%)) enhanced the subjects' intoxication when compared with THC alone (8 mg), but a 1:20 THC:CBD ratio (8 mg THC (1.6%)/400 mg CBD (80%)) reduced the subjects' intoxication when compared with THC alone (8 mg) (van de Donk et al., 2019). ...
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... Patients with chronic pain (CP) often describe their everyday bodily sensations as a knife being stabbed into the back, a bad sunburn that won't go away, metal filings under the skin, an open wound, or an electric shock. CP is the debilitating side-effect of numerous diseases and conditions, including cancer 1 , peripheral neuropathy [2][3][4][12][13][14] , and fibromyalgia [3][4][5] . CP affects more than 1.5 billion people around the world 6 and 64% of American adults over the age of 30 7 . ...
... Medical cannabinoids have shown to have some analgesic effects [2][3][4][5]8,13,14 and the potential to help individuals with CP reduce their opioid intake 9,11 . However, cannabis's history as a recreational drug has led to concerns about its efficacy and safety from physicians, patients, and the public, making its implementation as an established treatment option slow. ...
... The cannabis plant (Cannabis sativa) contains hundreds of cannabinoids that interact with CB1 receptors in the central nervous system 5,13,14 and CB2 receptors on immune cells throughout the body 5,13 . The major cannabinoid is ∆ 9tetrahydrocannabinol (THC), which is responsible for the "drug high" associated with cannabis use 5 . ...
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... Twenty patients were randomly divided into groups: bedrocan (22% THC, <1% CBD), bediol (6.3% THC, 8% CBD), bedrolite (<1% THC, 9% CBD), or placebo. Vaporized cannabis or placebo was administered on four occasions with a 2-week washout between treatments [34]. Spontaneous pain NRS scores were not significantly different between groups, but 18 patients receiving bediol reported a 30% reduction in spontaneous pain (p = 0.01) [34]. ...
... Vaporized cannabis or placebo was administered on four occasions with a 2-week washout between treatments [34]. Spontaneous pain NRS scores were not significantly different between groups, but 18 patients receiving bediol reported a 30% reduction in spontaneous pain (p = 0.01) [34]. Using an algometer to quantify pressure tolerance over the adductor pollicis muscle, bediol, and bedrocan enhanced the pressure threshold (bediol: increase from 9 to 11 kgf, p < 0.001; bedrocan: increase from 7 to 9 kgf, p = 0.006) [34,35]. ...
... Spontaneous pain NRS scores were not significantly different between groups, but 18 patients receiving bediol reported a 30% reduction in spontaneous pain (p = 0.01) [34]. Using an algometer to quantify pressure tolerance over the adductor pollicis muscle, bediol, and bedrocan enhanced the pressure threshold (bediol: increase from 9 to 11 kgf, p < 0.001; bedrocan: increase from 7 to 9 kgf, p = 0.006) [34,35]. The electrical pain test, assessed using two electrodes superior to the right medial malleolus, showed no effect of bedrocan or bediol electrical pain threshold [34,36]. ...
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... 4 Although the AE rates of sublingual or smoked or vaped MC declined from 40% after a month of treatment to 30% a year later, 4 in the current study, AEs declined from 34% during the titration phase to almost none during the maintenance phase, which ranged from 3 to 15 months. In a study on patients with fibromyalgia treated by a single vaporizer session of MC from the Bedrocan cultivar, which is the cultivar used for the VCs of the inhaler, 80% of the treated patients reported psychoactive effects, 11 whereas in our study, only 10% reported psychoactive AEs, such as anxiety and restlessness. Hence, MC treatment using the inhaler seems similar to traditional MC for effectiveness, but superior regarding safety, while exposing the patients to very low doses of aerosolized D 9 -THC. ...
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... In 1 trial, different types of inflorescences were administered to evaluate the most efficacious ratio of THC to CBD concentrations against pain. (Pretzsch, et al., 2019b;Solowij, et al., 2019;Van de Donk, et al., 2019;Abrams, et al., 2020;Farokhnia, et al., 2020;Liu, et al., 2020;Lopez, et al., 2020;Thompson, et al., 2020;Naftali, et al., 2021a;Anderson, et al., 2021;Aran, et al., 2021;Naftali, et al., 2021b) ...
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... In one small randomized controlled trial (n = 29), treatment with nabilone provided marginally better sleep compared with amitryptiline [96], and in another (n = 40) showed a significant decrease in pain and anxiety vs placebo [97]. More recently, a randomized controlled trial (n = 20) showed that inhaled pharmaceutical-grade cannabis containing THC and CBD reduced pain [98]. Inhaled pharmaceutical-grade cannabis containing primarily THC increased tolerance to pressure pain in this study. ...
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... Therefore, it is important to supervise and regulate the consumption of medical cannabis. In the majority of clinical studies exploring medical cannabis, exclusion criteria included history of psychiatric disorders (Collin et al., 2007;Wallace et al., 2015;van de Donk et al., 2019). In addition to the respiratory adverse effects, cardiovascular complications are poorly known but also reported with the use of cannabis. ...
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... In contrast a 2.5 mg sublingual CBD spray for 8 weeks did not improve chronic pain on a visual analog score in patients with chronic pain primarily due to MS [37]. CBD has also been shown to lack analgesic effect in fibromyalgia [38]. These studies are limited by the small size and low dose of CBD used. ...
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... A dysregulated ECS activity as a consequence of genetic and/or epigenetic alterations may result in several neuropsychiatric disorders. A synopsis of these experimental trials illustrate the complex behavior of inhaled cannabinoids and the shortcomings in an attempt to gain clinically relevant information about longterm treatment of chronic pain states with cannabinoids [107]. ...
... The absorption and the pharmacokinetic profile of CBD and THC after vaporization are almost identical. In patients, a pharmacokinetic profile was established following the administration of Bedrolite ® , a CBD-focused cannabis strain [107]. Vaporization of Bedrolite ® with 18.4 mg CBD and less than 1 mg of THC was inhaled. ...
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