Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia

Beal, Jeffrey E.; Olson, Richard R.; Lefkowitz, Lewis B.; Laubenstein, Linda; Bellman, Paul; Yangco, Bienvenido G.; Morales, Javier; Murphy, Robert L.; Powderly, William G.; Plasse, Terry F.; Mosdell, Kristen W.; Shepard, Kirk V.

doi:10.1016/s0885-3924(97)00038-9

Cited by 180 publications

(113 citation statements)

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“…1 Such historical anecdotal reports have provided the rationale for introducing the component of C. sativa, D 9 -tetrahydrocannabinol (THC) (known as Dronabinol) in clinical trials, in order to stimulate appetite and to reduce the weight loss in cachectic states associated with AIDS or malignant tumors. 2,3 This relatively recent clinical development in the therapeutic use of THC was anticipated by a long series of studies carried out in animals and humans to investigate the putative orexigenic effects of THC or Cannabis extracts. 1 …”

Section: Introductionmentioning

confidence: 99%

How many sites of action for endocannabinoids to control energy metabolism?

et al. 2006

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The promising results obtained by clinical trials using Rimonabant to tackle visceral obesity and related disorders recently promoted a remarkable impulse to carry out detailed investigations into the mechanisms of action of endocannabinoids in regulating food intake and energy metabolism. The endocannabinoid system has been known for many years to play an important role in the modulation of the neuronal pathways mediating the rewarding properties of food. However, in the last few years, with the advanced understanding of the crucial role of the hypothalamic neuronal network in the regulation of appetite, several studies have also directed attention to the orexigenic role of the endocannabinoid system, substantiating the well known appetite stimulating properties of derivatives of Cannabis sativa. Furthermore, the last 2 years have seen a number of relevant publications emphasizing the role of endocannabinoids as significant players in various peripheral metabolic processes. To date, the roles of the endocannabinoid system in influencing energy metabolism have proved to be more complex than was formerly believed. However, the diverse ability to modulate both central and peripheral processes highlights the pivotal involvement of the endocannabinoid system in the control of metabolic processes. This review describes the roles of endocannabinoids and the cannabinoid type 1 receptor (CB1) in the control of energy balance.

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Section: Introductionmentioning

confidence: 99%

How many sites of action for endocannabinoids to control energy metabolism?

et al. 2006

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“…In the 1990 s, clinical trials indicated that dronabinol could improve appetite and increase weight in cancer cachexia [68] and was useful in improving the nutritional status and appetite in persons with advanced HIV disease and AIDS wasting [69][70][71]. The FDA approved dronabinol as an appetite stimulant for AIDS related weight loss in 1992.…”

Section: Results Of Earlier Research With Cannabis Thc and Its Syntmentioning

confidence: 99%

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

Grant

Cahn

2005

Clinical Neuroscience Research

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The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control.

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“…A dose of 2.5 mg THC, corresponding to 0.04 mg THC/kg body weight (b.w.) (using a 60 kg body weight) was identified from human studies (Beal et al, 1997;BgVV, 1997BgVV, , 2000Ramaekers et al, 2004) as the LOEL for psychotropic effects (including euphoria, dizziness, thinking abnormalities and somnolence, reduction in performance including reaction time, and memory function) after either single or repeated exposure. A provisional maximum tolerable daily intake (PMTDI) of 0.0004 mg THC /kg b.w.…”

Section: Previous Assessmentsmentioning

confidence: 99%

“…In 94 late-stage AIDS patients who previously participated in the 6-week study mentioned above (Beal et al, 1995) effects of long-term (12 months) oral treatment with Δ 9 -THC were investigated (Beal et al, 1997). Ninety four patients entered the study, their prior marijuana use was in the same range as in the preceding study (Beal et al, 1995).…”

Section: Clinical Studies In Patients Treated With δmentioning

confidence: 99%

Scientific Opinion on the risks for human health related to the presence of tetrahydrocannabinol (THC) in milk and other food of animal origin

2015

EFS2

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The European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the risks for human health related to the presence of tetrahydrocannabinol (THC) in milk and other food of animal origin. THC, more precisely delta-9-tetrahydrocannabinol (Δ 9 -THC) is derived from the hemp plant Cannabis sativa. In fresh plant material, up to 90 % of total Δ 9 -THC is present as the non-psychoactive precursor Δ 9 -THC acid. Since few data on ∆ 9 -THC levels in foods of animal origin were available, the Panel on Contaminants in the Food Chain (CONTAM Panel) estimated acute human dietary exposure to ∆ 9 -THC combining different scenarios for the presence of ∆ 9 -THC in hemp seed-derived feed materials. Acute exposure to ∆ 9 -THC from the consumption of milk and dairy products ranged between 0.001 and 0.03 µg/kg body weight (b.w.) per day in adults, and 0.006 and 0.13 µg/kg b.w. per day in toddlers. From human data, the CONTAM Panel concluded that 2.5 mg Δ 9 -THC/day, corresponding to 0.036 mg Δ 9 -THC/kg b.w. per day, represents the lowest observed adverse effect level. By applying an overall uncertainty factor of 30, an acute reference dose (ARfD) of 1 μg Δ 9 -THC/kg b.w. was derived. The exposure estimates are at most 3 % and 13 % the ARfD, in adults and toddlers, respectively. The CONTAM Panel concluded that exposure to ∆ 9 -THC via consumption of milk and dairy products, resulting from the use of hemp seed-derived feed materials at the reported concentrations, is unlikely to pose a health concern. A risk assessment resulting from the use of whole hemp plant-derived feed materials is currently not feasible due to a lack of occurrence data. The CONTAM Panel could also not conclude on the possible risks to public health from exposure to ∆ 9 -THC via consumption of animal tissues and eggs, due to a lack of data on the potential transfer and fate of ∆ 9 -THC. Tetrahydrocannabinol, more precisely delta-9-tetrahydrocannabinol (Δ 9 -THC) is the most relevant constituent derived from the hemp plant Cannabis sativa. Four stereoisomers of Δ 9 -THC are possible, with (-)-trans-Δ 9 -THC being the only naturally occurring isomer. Delta-9-tetrahydrocannabinolic acid, which is found in the growing and harvested plant, is the biosynthetic precursor of Δ 9 -THC. Besides 2-COOH-Δ 9 -THC, which in this opinion is referred to as Δ 9 -THCA-A, another positional isomer, 4-COOH-Δ 9 -THC, denoted as Δ 9-THCA-B, may also occur in the hemp plant. In fresh plant material of C. sativa, up to 90 % of the 'total' Δ 9 -THC is present as the non-psychoactive precursor Δ 9 -THCA-A. The rate and extent of transformation of the precursor acids into Δ 9 -THC in the plant material is dependent on physical effects, in particular temperature. In addition to Δ 9 -THC, C. sativa preparations may contain at least 60 other cannabinoids, several of which are biologically active. This risk assessment does not evaluate the exposure and associated risks of cannabis used as a medicinal drug or for recreational purposes, but as requested in the ter...

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Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia

Cited by 180 publications

References 14 publications

How many sites of action for endocannabinoids to control energy metabolism?

How many sites of action for endocannabinoids to control energy metabolism?

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

Scientific Opinion on the risks for human health related to the presence of tetrahydrocannabinol (THC) in milk and other food of animal origin

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