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Abstract

In the present study, we investigated the effects of cannabidiol (CBD) on plasma prolactin, growth hormone and cortisol of 11 normal volunteers who received placebo or CBD at the doses of 300 mg (N = 7) or 600 mg (N = 4), po, in a double-blind manner during two experimental sessions separated by an interval of at least one week. The sessions were held in the morning and consisted of blood collection and application of self-evaluation scales before and after drug injection (-35 to 180 min). Hormonal measurements were performed by radioimmunoassay. Basal prolactin (11.5 +/- 4.3 ng/ml) and growth hormone (1.5 +/- 0.7 ng/ml) levels were unchanged after placebo and CBD. In contrast, plasma cortisol levels decreased significantly during the placebo sessions (basal measurement = 11.0 +/- 3.7 micrograms/dl; 120 min after placebo = 7.1 +/- 3.9 micrograms/dl), in agreement with the normal circadian rhythm of this hormone. This decrease in cortisol levels was significantly attenuated after CBD (basal measurement = 10.5 +/- 4.9 micrograms/dl; 120 min after 300 mg CBD = 9.9 +/- 6.2 micrograms/dl; 120 min after 600 mg CBD = 11.6 +/- 11.6 micrograms/dl). CBD was also found to have a sedative effect as determined by the self-evaluation scales. The present results suggest that CBD interferes with cortisol secretion.
... Additionally, CBD (300 mg) has been shown to induce changes in glucocorticoids as cortisol in humans (Zuardi A. W. et al., 1993), one of the primary homeostatic regulators of the inflammatory response to injury (Yeager et al., 2010). This is supported by a recent narrative review in sports, suggesting the potential anti-inflammatory effect in humans and the possible role in the performance of the athletes . ...
... Cannabidiol has been commonly used for its analgesic properties (Kogan and Mechoulam, 2007) in a variety of pain disorders (Starowicz and Finn, 2017). CBD consumption could exhibit a beneficial effect over edema and hyperalgesia (Burstein, 2015;Hill et al., 2017), acting directly on the central nervous system and leading to sedative effects (Zuardi A. W. et al., 1993). The idea of considering CBD as an antinociceptive agent is based on the efficiency of treating the pain associated with proinflammatory cytokine release due to the activation of Vanilloid receptors, provoking antinociceptive effects and reducing the perception of pain (Booz, 2011). ...
... Cannabidiol (300-400 mg) intake seems to have sedative effects on humans apparently acting directly on the central nervous system (Zuardi A. W. et al., 1993), supported by the idea that CBD exhibited a beneficial action over edema and hyperalgesia (Burstein, 2015;Hill et al., 2017). In this regard, drugs and substances such as Sativex, THC, and CBD are approved for the treatment of both central and peripheral neuropathic pain. ...
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The use of cannabidiol (CBD) among athletes is becoming extensive and frequent. This could be due to its elimination of CBD from the list of prohibited substances by federations and international institutions of sport. Also, CBD legalization, and production and commercialization allowance could rise it intake. This situation, despite the fact that the use and commercialization of cannabinoids has not ceased, has fueled the race to study their properties, benefits and risks for health and performance in athletes. Although there is evidence that suggests some beneficial properties such as anxiolytics, antidepressants, anti-inflammatory, antioxidants among others, the evidence presented so far is neither clear nor conclusive. In fact, there is a great gap in knowledge regarding the physiological pathways that explain the role of CBD in sports performance. This mini-review aims to expose the evidence suggesting that CBD has the potential to be used as part of strategies to recover from fatigue and muscle damage related to physical and cognitive exertion in sport.
... This survey found that those with current insomnia and greater sleep latency were significantly more likely to report using strains of cannabis with higher concentrations of CBD [167]. There are a few studies including case reports [139,168], case series [140], and randomized controlled trials [169,170] that indicate that CBD may be efficacious in promoting sleep. Yet, there is some contention in the literature, with some studies suggesting CBD has a stimulating or alerting effect [171,172], and others suggest CBD has a sedating effect [169,170] and one which found no effect in terms of sleepiness [173]. ...
... There are a few studies including case reports [139,168], case series [140], and randomized controlled trials [169,170] that indicate that CBD may be efficacious in promoting sleep. Yet, there is some contention in the literature, with some studies suggesting CBD has a stimulating or alerting effect [171,172], and others suggest CBD has a sedating effect [169,170] and one which found no effect in terms of sleepiness [173]. There is a need for research into the potential effects of CBD on sleep in cancer patients, since the benefits of improved sleep would be tremendous. ...
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The plant Cannabis sativa has been in use medicinally for several thousand years. It has over 540 metabolites thought to be responsible for its therapeutic effects. Two of the key phytocannabinoids are cannabidiol (CBD) and tetrahydrocannabinol (THC). Unlike THC, CBD does not have potentially intoxicating effects. Preclinical and clinical research indicates that CBD has a wide range of therapeutic effects, and many of them are relevant to the management of cancer. In this article, we explore some of the potential mechanisms of action of CBD in cancer, and evidence of its efficacy in the integrative management of cancer including the side effects associated with its treatment, demonstrating its potential for integration with orthodox cancer care.
... Our estimation of sample size was based on prior studies that assessed the effects of CBD on anxiety produced by public speaking with the Visual Analog Mood Scale (VAMS). 13,14 Considering the average result for the anxiety factor of the VAMS scale, we can expect a significant difference of 10.8 mm and a standard deviation of 13 mm for the placebo group and 8.5 mm for the CBD group. Assuming 80% test power, to detect a difference at the 5% significance level, the minimum number of volunteers was established as 15 per group. ...
... The SPST was developed and validated by McNair et al. 19 Detailed descriptions of the protocol are available elsewhere. 13,18,20 Briefly, the subject is requested to prepare a speech and speak in front of a video camera. Before and after each procedure, the subjects complete the rating scales. ...
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Objective: To compare plasma concentrations of cannabidiol (CBD) following oral administration of two formulations of the drug (powder and dissolved in oil), and to evaluate the effects of these distinct formulations on responses to emotional stimuli in healthy human volunteers. Methods: In a randomized, double-blind, placebo-controlled, parallel-group design, 45 healthy male volunteers were randomly assigned to three groups of 15 subjects that received either 150 mg of CBD powder; 150 mg of CBD dissolved in corn oil; or placebo. Blood samples were collected at different times after administration, and a facial emotion recognition task was completed after 150 min. Results: There were no significant differences across groups in the subjective and physiological measures, nor in the facial emotion recognition task. However, groups that received the drug showed statistically significant differences in baseline measures of plasma CBD, with a significantly greater difference in favor of the oil formulation. Conclusion: When administered as a single 150-mg dose, neither formulation of oral CBD altered responses to emotional stimuli in healthy subjects. The oil-based CBD formulation resulted in more rapid achievement of peak plasma level, with an approximate fourfold increase in oral bioavailability.
... Cannabidiol (CBD) is one of the major non-psychoactive constituents found in the plant Cannabis sativa L. (marijuana) (Adams et al., 1940;Campos et al., 2012;Huestis, 2007). Beneficial effects of CBD in neuronal physiology have been reported (Grotenhermen, 2003), such as neuroprotective activity via anti-inflammatory and anti-oxidative properties (Costa et al., 2004;Hampson et al., 1998;Silvestro et al., 2020;Ward et al., 2014), sedative effects that decrease anxiety (Crippa et al., 2004;Zuardi et al., 1993), and an anti-epileptic effect that reduces seizure frequency (Elliott et al., 2019;Lattanzi et al., 2018). Recently, CBD has also been implicated to have potentially positive effects for treating ischemic stroke (Hayakawa et al., 2010), psychosis, such as schizophrenia (Batalla et al., 2019;McGuire et al., 2018), and neurodegenerative diseases, such as Alzheimer's disease (Libro et al., 2017;Watt and Karl, 2017). ...
Article
Cannabidiol (CBD) is a major cannabinoid present in extracts of the plant Cannabis sativa (marijuana). While the therapeutic effects of CBD on epilepsy have been demonstrated, less is understood regarding its potential adverse effects. Recent studies revealed that CBD induced toxicity in the male reproductive system of animal models. In this study, we used TM4, an immortalized mouse Sertoli cell line, and primary human Sertoli cells to evaluate the toxicities of CBD and its main metabolites, 7-carboxy-CBD and 7-hydroxy-CBD. CBD induced concentration- and time-dependent cytotoxicity in mouse and human Sertoli cells, which mainly resulted from the inhibition of the G1/S-phase cell cycle transition. CBD also inhibited DNA synthesis and downregulated key cell cycle proteins. Moreover, CBD reduced the mRNA and protein levels of a functional marker, Wilms’ tumor 1. Similar to CBD, 7-carboxy-CBD and 7-hydroxy-CBD inhibited cellular proliferation and decreased DNA synthesis. 7-Carboxy-CBD was less cytotoxic than CBD, while 7-hydroxy-CBD showed comparable cytotoxicity to CBD in both mouse and human Sertoli cells. Compared to mouse Sertoli cells, CBD, 7-hydroxy-CBD, and 7-carboxy-CBD were more cytotoxic in human Sertoli cells. Our results indicate that CBD and its main metabolites can inhibit cell proliferation in mouse and human Sertoli cells.
... For years, scientists researched fatty acids and their immunomodulatory effects, as they give rise to inflammatory mediators such as prostaglandins and leukotrienes, and alter the membrane fluidity of immune cells [9,10]. Additionally, trace amounts of CBD (cannabidiol) could potentially be found in the oil, which can also have anti-inflammatory effects [11][12][13]. To our knowledge, comprehensive studies describing the effects of different levels of HSM supplementation on the immune responses of animals are lacking. ...
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The objective of this study was to evaluate the effect of varying levels of hempseed meal supplementation on antibody and cell-mediated immune responses, as well as the expression of some of the important immunoregulatory cytokines. Treatments consisted of hempseed meal supplementation at 0 (control), 10, 20, and 30% of the total diet. Goats were randomly assigned to one of the four treatments n = 10. Cell-mediated immune response was evaluated on day 59 of the feeding period by measuring skinfold thickness at 24 h following intradermal injection of phytohemagglutinin. A significant increase in skinfold thickness was observed with increasing levels of supplementation as compared to that of the control group. Serum antibody titers to chicken ovalbumin were not significantly different between treatment groups. Cytokine concentrations of IL-6 increased linearly with increasing level of supplementation (p < 0.05), contrarily to the linear decrease that was observed for TNF-α (p < 0.05). Although IL-2 tended to increase with the 10 and 30% levels of supplementation (p < 0.07), the result was not significant, and no significant differences were obtained with respect to IL-4 concentrations. Cytokine gene expression values measured by RT-PCR, however, demonstrated some significant differences. HSM supplementation had no significant effect on the expression of IL-2 or IL-6. However, significant differences were observed with the 30% supplementation for IL-4 and TNF-α as compared to that of the control group (p < 0.05). IL-4 was down regulated for the 10 and 20% treatment groups but was upregulated for the 30% treatment group. TNF-α was downregulated in the 10% but upregulated for the 20 and 30% treatment groups. No significant differences were observed for the serum cortisol concentration or white blood cell counts. These results suggested that hempseed meal supplementation may improve cell-mediated immune response while having no effect on antibody-mediated immune response. However, more research needs to be conducted to determine the most efficacious inclusion rate.
... A high dose of CBD increases the duration of sleep [120]. Another study has shown a sedative effect following oral use of CBD [121]. CBD increases the duration of sleep in subjects with insomnia [122]. ...
Article
Cannabis sativa (Marijuana) has a long history as a medicinal plant and Δ9-tetrahydrocannabinol (Δ9-THC) is the most active component in this plant. Cannabinoids are interesting compounds with various modulatory effects on physiological processes and cognitive functions. The use of cannabinoids is a double-edged sword, because they induce both adverse and therapeutic properties. One of the most important roles of cannabinoids is modulating sleep-wake cycle. Sleep, its cycle, and its mechanism are highly unknown. Also, the effects of cannabinoids on sleep-wake cycle are so inconsistent. Thus, understanding the role of cannabinoids in modulating sleep-wake cycle is a critical scientific goal. Cannabinoids interact with many neurotransmitter systems. In this review article, we chose serotonin due to its important role in regulating sleep-wake cycle. We found that the interaction between cannabinoids and serotonergic signaling especially in the dorsal raphe is extensive, unknown, and controversial.
... In experimental studies, CBD has been safely administered to healthy humans in doses ranging from 15 mg to 600mg (oral) per day (20,(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97) alone and in combination with THC and is known to have been tolerated well with no significant adverse effects. Previous studies have also demonstrated that IV CBD is well . ...
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Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the principal phyto-cannabinoids in the cannabis plant. The differential and possibly antagonistic effects of these compounds on specific brain and behavioral responses, and the mechanisms underlying their effects have generated extensive interest in pre-clinical and clinical neuroscience investigations. In this double-blind randomized placebo-controlled counterbalanced human laboratory experiment, we examined the effects of three different dose ratios of CBD: THC (1:1, 2:1 and 3:1) on neural noise, an electrophysiological biomarker of psychosis known to be sensitive to cannabinoids as well as subjective and psychotomimetic effects. Interestingly, the lowest CBD:THC ratio (1:1) resulted in maximal attenuation of both THC induced psychotomimetic effects (PANSS positive - ATS = 7.83, df = 1, pcorr = 0.015) and neural noise (ATS = 8.83, df = 1, pcorr = 0.009) with an inverse-linear dose response relationship. Further, in line with previous studies, addition of CBD did not reduce the subjective experience of THC induced high (p > 0.05 for all CBD doses). These novel results demonstrate that CBD attenuates THC induced subjective and objective effects relevant to psychosis- but in a dose/ratio dependent manner. Given the increasing global trend of cannabis liberalization and application for medical indications, these results assume considerable significance given the potential dose related interactions of these key phyto-cannabinoids.
... The lack of effect on overall daily activity and sleep quality was unexpected based on previous reports of the sedative and hypnogenic effects of CBD in rodent, human, and canine models. In humans and rats, CBD doses ranging from ∼2 to 40 mg/kg BW/day have been reported to induce sedative effects, improve sleep quality, and increase total sleep time (41,46,47). However, more recent work has reported CBD to have no influence on the sleep cycle in humans (48), and others argue that CBD by itself does not produce sedative effects but rather modulates the sedative effect of 9 -tetrahydrocannabinol (THC), even if THC is only present in minute amounts (42,49,50). ...
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Growing public interest in the use of cannabidiol (CBD) for companion animals has amplified the need to elucidate potential impacts. The purpose of this investigation was to determine the influence of CBD on the daily activity of adult dogs. Twenty-four dogs (18.0 ± 3.4 kg, 9 months−4 years old) of various mixed breeds were utilized in a randomized complete block design with treatments targeted at 0 and 2.5 mg (LOW) and at 5.0 mg (HIGH) CBD/kg body weight (BW) per day split between two treats administered after twice-daily exercise (0700-0900 and 1,700-1,900 h). Four hours each day [1,000-1,200 h (a.m.) and 1,330-1,530 h (p.m.)] were designated as times when no people entered the kennels, with 2 h designated as Quiet time and the other 2 h as Music time, when calming music played over speakers. Quiet and Music sessions were randomly allotted to daily a.m. or p.m. times. Activity monitors were fitted to dogs' collars for continuous collection of activity data. Data were collected over a 14-day baseline period to establish the activity patterns and block dogs by activity level (high or low) before randomly assigning dogs within each block to treatments. After 7 days of treatment acclimation, activity data were collected for 14 days. Data were examined for differences using the MIXED procedure in SAS including effects of treatment, day, session (Quiet or Music), time of day (a.m. or p.m.), and accompanying interactions. CBD (LOW and HIGH) did not alter the total daily activity points (P = 0.985) or activity duration (P = 0.882). CBD tended (P = 0.071) to reduce total daily scratching compared with the control. Dogs were more active in p.m. sessions than in a.m. sessions (P < 0.001). During the p.m. session, dogs receiving HIGH tended (P = 0.091) to be less active than the control (CON). During the a.m. and p.m. sessions, CBD reduced scratching compared with CON (P = 0.030). CBD did not affect the activity duration during exercise periods (P = 0.143). These results indicate that, when supplemented with up to 4.5 mg CBD/kg BW/day, CBD does not impact the daily activity of adult dogs, but may exert an antipruritic effect.
Article
This phase II clinical trial investigates a one-time oromucosal dose of tetrahydrocannabinol/cannabidiol (THC/CBD) in 23 patients with indolent leukemic B cell lymphomas. Primary endpoint was a significant reduction in leukemic B cells. Grade 1 − 2 adverse events were seen in 91% of the patients; most common were dry mouth (78%), vertigo (70%), and somnolence (43%). After THC/CBD a significant reduction in leukemic B cells (median, 11%) occurred within two hours (p = .014), and remained for 6 h without induction of apoptosis or proliferation. Normal B cells and T cells were also reduced. CXCR4 expression increased on leukemic cells and T cells. All effects were gone by 24 h. Our results show that a single dose of THC/CBD affects a wide variety of leukocytes and only transiently reduce malignant cells in blood. Based on this study, THC/CBD shows no therapeutic potential for indolent B cell lymphomas (EudraCT trial no. 2014-005553-39).
Chapter
Good sleep is vital for good health, and poor sleep, in particular insomnia, is associated with a range of poor health outcomes. Sleep disorders are common and a key reason why people self-medicate with cannabis. We have two key biological mechanisms which work together to regulate our sleep-wake cycle, the processes of sleep-wake homeostasis and our circadian rhythms. The endocannabinoid system is involved in the circadian sleep-wake cycle, including maintenance and promotion of sleep, and may provide the link between the circadian regulation systems and the physiological process of sleep. Cannabis has been used for centuries to treat sleep disorders. Preclinical and clinical evidence indicate that cannabidiol and tetrahydrocannabinol may have a role to play in the treatment of sleep disorders.
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