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Cannabinoid Medicine

‘Whole plant’ cannabis has been used in popular medicine for thousands of years.  Despite advances in cultivation techniques, the variability of the compositions of cannabis flowers from plants with different genetics or grown in different conditions creates unpredictable or contradictory clinical datasets.  Therefore, despite the potential benefits, there is a need for a more predictable drug discovery process to ensure that a cannabinoid medicine targets receptors in the body both effectively and exclusively and does this the same way every time a patient takes it.   

What are Cannabinoids?

The word cannabinoid refers to molecules that interact with cannabinoid receptors. Cannabinoids are produced by human beings (endocannabinoids) and all other mammals, and also in plants of different genera (phytocannabinoids), most notably by Cannabis sp.

Research has found that the cannabis plant produces over 100 active cannabinoids referred to as phytocannabinoids (“pCBs”). The two best known cannabinoids are delta-9-tetrahydrocannabinol (“THC”) and cannabidiol (“CBD”). The most widely recognised is THC, the compound that is primarily responsible for the psychoactive effects of cannabis. However, a recent increase in the use of cannabis extracts has resulted in the growing popularity of CBD and also rarer cannabinoids (e.g., Cannabigerol or Cannabidiolic acid).  In the drug discovery process at OCT, we are focused on 3 types of cannabinoids:  unmodified pCBs, chemically modified pCBs with improved drug-like characteristics and novel chemical entities (NCEs) with cannabinoid receptor selectivity.

The Endocannabinoid System

The Endocannabinoid System (ECS) is a biological system that plays an important role in many physiological processes in the body to maintain the balance between our physical and mental health including regulating pain, mood, memory, sleep, appetite, and the immune response to cancer.  Where this balance becomes disrupted by disease, the aim is to restore it with cannabinoid-based treatments.

 

Primarily in neuronal cells; also in peripheral organs and tissue

CB1 modulation impacts pain, motor control, memory & behaviour

CB1 mediates psychoactivity

Therapeutic intervention: neuronal and motor neural conditions, neuropathic pain, metabolism; cancers

Abundantly expressed in the periphery: immune cells & lymphoid organs; lungs; heart; bones; gastrointestinal and liver

Receptor stimulation does not produce psycho-active effects

Thus, CB2 agonists appeal as therapeutics in auto-immunity; inflammatory disorders; chronic pain and cancer

 

ECS receptors are found in the brain and peripheral nervous system, but also in many other cells throughout the body. The most studied and prominent are the CB1 and CB2 receptors.

There is a growing body of evidence supporting the medical potential of phytocannabinoids and cannabinoid derivatives in restoring the optimal function of the endocannabinoid system when it becomes disrupted by disease.  

Through medicinal chemistry and screening, cannabinoid derivatives and other new chemical entities can be designed to target single receptors. OCT461201, for example, is highly selective for CB2. Targeting CB2 has many benefits, including anti-neuroinflammatory and nociceptive properties, without any psychoactive side-effects.  OCT130401 combines two different cannabinoids which are known for their analgesic and anti-inflammatory properties. The combination aims to provide both immediate pain relief and long-term amelioration of the painful conditions where inflammation plays a role.