The next time you are sitting on a park bench listening to the 25th anniversary edition of Tull’s Aqualung, ponder this: why do humans have endogenous ligands in their brains that resemble opium and marijuana biomolecules? How do these systems interact? What are the medical implications? The answers lie in addiction and reward pathways.

In a previous series I explored some of the uses of cannabis in treating addiction. It turns out that cannabis is, in many ways, an indispensable tool in the treatment of addictions to psychostimulants (cocaine, methamphetamine), nicotine, opiates, and even alcohol.

How is it possible that this humble weed can have such diverse applications in treating addiction? After all, alcohol, cocaine, and methamphetamine stimulate very different brain receptors than nicotine or the opiate class of drugs.

Where is the connection between these vastly divergent systems? In this series I will explore the newly discovered role that the endocannabinoids play in pleaser seeking and the reward pathway.


Scientists have known for some time that addiction is closely tied into the brain’s “reward system,” and sugar cravings to Lustig’s “hedonic pathway,” within special areas of the brain. These systems are rich in dopamine containing neurons. When you hear dopamine, think pleasure.

Dopamine is one of many neurotransmitters which are used to talk to other brain regions within this complex matrix. When someone snorts cocaine, smokes pot, or uses heroin, the same pleasure/reward system becomes activated altering brain levels of dopamine. This is part of the “high” that drug seekers receive-the reward for using that drug.

A dopamine depleted person is often times labelled a “thrill seeker,” because the thrill-such as sky diving-releases a surge of dopamine helping to restore balance within that person’s brain. Part of the runner’s high is dopaminergic. This is what keeps people coming back for more too.

The brain’s reward circuitry consists of an “in series” circuit of dopaminergic (DA) neurons in the ventral tegmental area (VTA), nucleus accumbens (Acb), and that portion of the medial forebrain bundle (MFB) which links the VTA and Acb. Drugs which enhance brain reward (and have derivative addictive potential) have common actions on this core DA reward system and on animal behaviors relating to its function. Such drugs enhance electrical brain-stimulation reward in this reward system; enhance neural firing and DA tone within it…it is now clear that cannabinoids activate these brain reward processes and reward-related behaviors in similar fashion to other reward-enhancing drugs[ref]Pharmacol Biochem Behav. 2005 Jun;81(2):263-84.[/ref].

Depending on the substance used other receptors then come into play to give the user the distinctive high that comes from that particular drug of abuse.

But it’s not quite that simple. While scientists know that opiates arouse the dopamine reward system they have learned recently that opiates also stimulate the endocannabinoid system and vice versa. They all share a role in this complex phenomenon. This cross talk helps explain how pot relieves pain, it acts as an opiate.

Cannabinoid agonists may also release endogenous opioids, and a functional interplay between the endocannabinoid and opioid systems in modulating analgesic responses has been suggested by numerous studies (Pugh et al., 1997; Manzanares et al., 1999a,b; Houser et al., 2000; Ibrahim et al., 2005; Tham et al., 2005; Vigano et al., 2005a,b; Williams et al., 2006)[ref]J Pharmacol Exp Ther. 1997 May;281(2):730-7[/ref].

As you can see this can be a good thing. Cannabis can help relieve pain by acting through the opiate system as well as through non-opiate pathways.

This also where addiction manifests because both the opioid and cannabinoid systems act in tandem with each other and directly on the reward system. When one repeatedly tweaks the reward apparatus one can expect the possibility of developing tolerance and addiction in about one third of heavy users.


Ever since humans have been using recreational drugs they have had problems with addiction. But what is addiction?

Drug abuse often leads to a complex pharmaco-dependent state which is defined by the term addiction. Addiction is considered as a neuropsychiatric disease. It develops from an initial recreational drug use, evolves toward compulsive drug-seeking behavior and excessive drug-intake with the appearance of negative emotional states such as anxiety or irritability when the drug is not accessible, and uncontrolled intake reaching a stage where the drug interferes with daily activities, despite the emergence of adverse consequences (Leshner, 1997; Everitt and Robbins, 2005; Robinson and Berridge, 2008; Koob, 2009). This pathological process develops in 15–30% of casual drug users…[ref]Katia Befort. Front Pharmacol. 2015; 6: 6.[/ref]

Once addicted to a drug the actual process restructures the brain often causing a near permanent change within the brain’s receptors. One of the brain regions most densely populated with both mu (opiate) and CB1 (cannabinoid) receptors are the regions rich in dopamine, the brain reinforcement/reward areas.

In part two we will explore the opioid and cannabinoid systems in greater detail as well as the functional interplay these systems have in the use of psychostimulants, nicotine and ethanol.