Cannabis and the Brain

THC affects all different parts of the brain, let’s take a look at how the different regions of the brain contribute to the effects of THC!

The Prefrontal Cortex:

The prefrontal cortex is highlighted in blue on a grey illustration of a brain.

The prefrontal cortex (PFC)is responsible for functions like decision-making, planning, and social behavior. When THC binds to CB1 receptors in this region, it modulates dopamine release and alters cognitive processes and judgment. The altered sense of time many people experience is because CB1 activity interferes with the PFC’s ability to collaborate with other brain regions to estimate time.

Effects: Impaired cognition and judgment, altered sense of time

  • Citation: Ranganathan, M., & D’Souza, D. C. (2006). The acute effects of cannabinoids on memory in humans: A review. Psychopharmacology, 188(4), 425-444. doi:10.1007/s00213-006-0508-y

Hippocampus

The hippocampus is highlighted in orange on a grey illustration of a brain.

The hippocampus is the part of the brain mostly responsible for memory formation and spatial navigation, and has a lot of CB1 receptors, which are modulated by THC. This interferes with learning and memory formation, which helps to explain cannabis-induced short term memory deficits! This is one region where THC can help with PTSD, as it helps to reduce emotional responses to traumatic memories.

Effects: Short term memory impairment

Citations: 

  • Volkow, N. D., Hampson, A. J., & Baler, R. D. (2014). Don’t Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward. Annual Review of Pharmacology and Toxicology, 54(1), 199-222. doi:10.1146/annurev-pharmtox-010611-134641
  • Passie, T., Emrich, H. M., Karst, M., Brandt, S. D., & Halpern, J. H. (2012). Mitigation of post-traumatic stress symptoms by Cannabis resin: A review of the clinical and neurobiological evidence. Drug Testing and Analysis, 4(7-8), 649-659. doi:10.1002/dta.1377

Amygdala

The amygdala is highlighted in red on a grey illustration of a brain.

The amygdala is an important brain region for emotion and fear processing. THC’s effects on CB1 receptors can have variable effects here, depending on dosage, environment, and individual susceptibility. It can either enhance or diminish fear responses. This is why for some, THC can cause anxiety or paranoia, while it de-stresses and relaxes others. 

Effects: Anxiety or relaxation

  • Citation: Phan, K. L., Angstadt, M., Golden, J., Onyewuenyi, I., Popovska, A., & de Wit, H. (2008). Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. Journal of Neuroscience, 28(10), 2313-2319. doi:10.1523/JNEUROSCI.5603-07.2008

Basal Ganglia and Cerebellum

The cerebellum is highlighted in pink and the basal ganglia is purple on a grey illustration of a brain.

These brain regions are important when it comes to motor control and coordination. CB1 receptor activation in these regions disrupts the normal release of neurotransmitters necessary for precise motor function, leading to slowed reaction times and clumsy motor function. This activation is beneficial for conditions like MS, where it has been shown to reduce spasms. It’s also one of the factors involved in the intense relaxation of “couch-lock”

Effects: Decreased motor coordination

  • Citation: Fernández-Ruiz, J., Hernández, M., & Ramos, J. A. (2010). Cannabinoid-Dopamine Interaction in the Pathophysiology and Treatment of CNS Disorders. Current Drug Targets, 11(4), 495-510. doi:10.2174/138945010791011948

Nucleus Accumbens

The hypothalamus is highlighted in cyan on a grey illustration of a brain.

The nucleus accumbens is a vital part of the brain’s reward system, and is involved in processing pleasure and reward. When THC stimulates dopamine release here, it leads to feelings of euphoria.. This is a great target for depression or chronic stress, as it enhances mood and decreases apathy. This same dopamine surge can be activated by food, music, and exercise.

Effects: Euphoria

  • Citation: Le Foll, B., & Goldberg, S. R. (2005). Cannabinoid and Opioid Interactions: Implications for Opiate Dependence and Withdrawal. Neuroscience & Biobehavioral Reviews, 29(1), 21-36. doi:10.1016/j.neubiorev.2004.06.009

Hypothalamus

The hypothalamus is highlighted in green on a grey illustration of a brain.

The hypothalamus helps to regulate appetite, sleep, and other basic functions. When THC binds to CB1 receptors here, it stimulates the release of ghrelin, a hunger hormone, and melatonin, a hormone related to the circadian-rhythm, or sleep cycles. This brain region is the reason THC causes the “munchies” and improves sleep!

Effects: Increased appetite, sleep regulation

  • Citation: Koch, J. E. (2001). Cannabinoid-induced feeding: Role of orexigenic and anorexigenic hypothalamic mediators. European Journal of Pharmacology, 423(1), 39-42. doi:10.1016/S0014-2999(01)01121-4

Brainstem

The brainstem is highlighted in blue on a grey illustration of a brain.

The brainstem controls automatic  functions necessary for survival, like breathing, heart rate, basic motor control, fight-or-flight responses, and aggression. This area (part of the oft-referred to “lizard brain”, since it maintains our most primitive functions) has relatively few CB1 receptors, so THC has minimal effect here, and, unlike alcohol, won’t shut down any of your life-sustaining functions. There are, however, CB1 receptors in the dorsal vagal complex within the brainstem, which suppress the release of neurotransmitters that trigger vomiting. This helps block nausea, and is especially known to help with chemotherapy, where toxins induce nausea and vomiting.

Effects: Nausea relief

  • Citation: Sharkey, K. A., Darmani, N. A., & Parker, L. A. (2014). Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system. European Journal of Pharmacology, 722, 134-146. doi:10.1016/j.ejphar.2013.09.068

Spinal Cord

The spinal cord is highlighted in green on a grey illustration of a brain.

The spinal cord is essential when it comes to THC’s effects on pain. All nerves in the body are routed through connections in the spinal cord, which acts as the superhighway to the brain—where their signals are analyzed and interpreted. There are a lot of CB1 receptors in the spinal cord, and when these are activated by THC, the pain signals traveling to the brain are dampened, leading to a lesser perception of pain. This is why chronic pain is the most pervasive condition treated by medical cannabis, and the reason it’s been used for pain relief for over 5,000 years!

Effect: Pain Relief

  • Citation: Atwal, S., Medina, I., & Lynch, J. (2019). Cannabinoids in pain management and palliative medicine. Cureus, 11(8), e5363. doi:10.7759/cureus.5363