The therapeutic use of CB1 receptor agonists (chemicals that bind directly to the receptor) like THC have been necessarily limited because of the psychoactive effects many of them produce. THC produces psychoactivity because it binds to CB1 receptors in the brain, where they are most abundant. While many people enjoy the effects of THC in cannabis, the effects can be strong enough to be limiting in a medical situation.
Although they are found mostly in the brain, recent evidence has suggested that CB1 receptor agonists could be used in the peripheral nervous system (the nerves in the rest of the body) for analgesia and countering the antagonistic effects of metabolic syndrome. Potentially, they can be used as anti-obesity drugs.
Here is the full scientific article if you wish to download it.
This paper assesses the risks and benefits of peripheral CB1 agonists and their possible uses. The conclusions are that there is significant potential for peripherally restricted CB1 agonists in therapies for a variety of conditions. These are very newly discovered and need to be explored more fully.
Recently, CB1 receptors full text have been found in the peripheral nervous system and tissues in levels that were not previously thought to exist. Preliminary data show that they are involved in lipid deposition (or where fats are concentrated), metabolic regulation, food intake, and peripheral pain.
Unfortunately, most of the current cannabinoid drugs that are available are blood-brain permeable. When they can pass through the blood-brain barrier, they can exert effects on the central nervous system. This is useful for some forms of analgesia and indeed recreation, but limits their use for peripheral conditions involving the endocannabinoid system because of the psychoactivity they cause.
A new class of peripherally restricted (i.e. will not pass through the blood-brain barrier into the central nervous system and therefore do not produce psychoactive effects) cannabinoids is in development. A few have already been shown to be effective CB1 agonists and have clinical applications.
Obesity is a difficult condition to treat because it is very complex, involving many processes and signalling pathways that are common to both the brain and the periphery. Most of the drugs that have been developed to treat obesity have had unwanted central nervous system effects, cannabinoids included. While cannabinoids are known to have a role in appetite, they have until now been restricted in their use because of the CNS effects.
The emergence of peripherally restricted cannabinoids could potentially have positive effects on appetite, and thus treat obesity, while not producing the psychoactivity that has until now made cannabinoid obesity therapy intolerable. Depression, anxiety, and psychoactivity are some of the side effects of CNS CB1 activation and are therefore worth avoiding.
Other metabolic disorders could be treated in a similar way. If a drug only affects the peripheral CB1 receptors, it can be used to interact with the complex metabolic systems that control homeostasis and metabolism in a tolerable way.
The peripheral CB1 receptors are potential targets for several common disorders and conditions. Obesity is a huge and growing problem and there are currently no effective drugs to treat it. Peripherally restricted CB1 agonists have been shown that in principle at least, they could have an effect on appetite and metabolism without the unwanted psychoactivity of CNS CB1 activation.