Medical Marijuana and Other Cannabinoids _____________________________________________________
smoked cannabis in the treatment or management of the dis- eases and conditions identified by the IOM for which cannabis has highest therapeutic potential [26]. A similar process began in Canada in 2001, with the goal of systematically investigat- ing cannabinoid safety and efficacy through preclinical and clinical trials. This was part of a larger effort by the Canadian government to better understand safe and effective medical cannabis use and was initiated in tandem with a centralized and controlled process of cannabis cultivation and distribu- tion to appropriate medical patients [27; 28]. The Netherlands government established the Office of Medicinal Cannabis (OMC) in 2000 to grow cannabis according to pharmaceutical standards and to implement a supply chain to distribute and dispense cannabis to patients and researchers [29].
sleep cycles, blood pressure, bone density, tumor surveillance, neuroprotection, and reproduction. The so-called “runner’s high” and the effects of osteopathic manipulative therapy and electroacupuncture are mediated by the ECS [32; 33]. The ECS is a system common to all vertebrates and many invertebrates and has been present in living organisms as far back as 600 million years. In the invertebrate species Hydra vulgaris , a primitive evolutionary throw-back to several hundred million years, feeding is mediated by the ECS. This discovery underscores the essential pro-survival function of the ECS that long pre-dates mammalian evolution, where the more recently evolved hypothalamic system regulates the survival function of appetite [28; 34].
CANNABINOID RECEPTORS CB1 Receptors
THE ENDOGENOUS CANNABINOID SYSTEM
CB1 receptors are the most abundant G-protein-coupled receptors in the brain and are expressed at lower densities in many peripheral tissues. CB1 receptors solely mediate the psychotropic and behavioral effects of cannabinoids and regu- late several peripheral processes, such as energy homeostasis, cardiovascular function, and reproduction [30; 35]. CB1 distribution in the brain matches the known pharmaco- dynamic effects of cannabinoids; CB1 activation prominently modulates cognition and memory, perception, control of motor function, and analgesia [36]. The location and relative density of CB1 receptors in the brain and function mediated by CB1 activation are outlined in Table 1 [37; 38; 39; 40].
The endogenous cannabinoid system (ECS) is a signaling sys- tem that includes cannabinoid receptors, endogenous receptor ligands (termed endocannabinoids), and their synthesizing and degrading enzymes [30]. Core functions of the ECS have been described as “relax, eat, sleep, forget, and protect,” shorthand for the diversity of processes involving the ECS [31]. The ECS regulates neuronal excitability and inflammation in pain cir- cuits and cascades and also helps regulate movement, appetite, aversive memory extinction, hypothalamic-pituitary-adrenal (HPA) axis modulation, immunomodulation, mood, wake/
CB1 RECEPTORS IN THE BRAIN
Brain Region
Function
Highest CB1 density Substantia nigra
Reward, addiction, movement Motor control and coordination
Cerebellum
Globus pallidus Caudate nucleus
Voluntary movements
Learning and memory system
Moderate CB1 density Cerebral cortex
Decision-making, cognition, emotional behavior
Putamen Amygdala
Movement, learning
Anxiety and stress, emotion and fear, pain
Hippocampus
Memory and learning
Lower CB1 density Hypothalamus
Body temperature, feeding, neuroendocrine function
Minimal or absent CB1 density Brain stem
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Medulla Thalamus Source: [37; 38; 39; 40]
Table 1
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