The most strident supporters of cannabis often expound the plant's beneficial properties, from the ephemeral mystical to the empirically medicinal. In recent years, opinions on the drug have begun to soften, and hypothesis-driven research continues to increase, with the intent of separating factual data from anecdotes. Now, a collection of investigators led by scientists at the Montreal Neurological Institute and Hospital—part of McGill University—have provided new information that seeks to improve our understanding of how cannabinoids, the active agent in marijuana, affect vision in vertebrates.
Using tadpoles as a model system for vision and visual development, the researchers employed a variety of techniques to test how the tiny amphibians reacted to visual stimuli after they had been exposed to increased levels of exogenous or endogenous cannabinoids. Exogenous cannabinoids are artificially introduced drugs, whereas endogenous cannabinoids occur naturally in the body.
Contrary to what they expected, the investigators found that activating cannabinoid signaling in tadpoles actually increased the activity in their retinal ganglion cells (RGCs), which are responsible for transmitting information about light detection from the eye to the brain. This was divergent from previous study results which found that cannabinoids typically work to reduce neurotransmission, not increase it.
“Initially you distrust yourself when you see something that goes against widely held ideas, but we tried the experiment so many times, using diverse techniques, and it was a consistent result,” explained senior study author Edward Ruthazer, Ph.D., professor of neurology and neurosurgery at the Montreal Neurological Institute of McGill University. “So then we knew we had to figure out what was going on. The first tendency is to want to ignore it. But it was such a strong effect—we knew there was something important here.”
Interestingly, the researchers found that one class of cannabinoid receptor, known as CB1R, plays a role in the suppression of chloride transport into the RGCs. When the receptor was activated, chloride levels were reduced, which hyperpolarizes the cell, making it able to fire at higher frequencies when stimulated. For the tadpoles, this meant they were able to detect dimmer objects in low light than when they had not been exposed to increased levels of cannabinoids.
“We identified a novel mechanism underlying a CB1R-mediated increase in retinal ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent inhibition of NKCC1 [Na+-K+-2Cl− cotransporter 1] activity,” the authors wrote. “Clomeleon imaging and patch clamp recordings revealed that inhibition of NKCC1 downstream of CB1R activation reduces intracellular Cl− levels in RGCs, hyperpolarizing the resting membrane potential.”
The findings from this study were published recently in eLife in an article entitled “Endocannabinoid Signaling Enhances Visual Responses through Modulation of Intracellular Chloride Levels in Retinal Ganglion Cells.”
While it’s too early to tell if cannabinoids have the same effect on human vision, there is anecdotal evidence in the scientific literature of cannabis ingestion improving night vision of Jamaican and Moroccan fishermen.
Yet, what is ultimately more interesting is that the researchers have stumbled upon a previously unknown role for cannabinoids in brain signaling. Now that therapeutic use of cannabinoids is becoming increasingly accepted by the medical community, the need for an accurate and thorough understanding of these chemicals' role in the brain is greater than ever.
“Our work provides an exciting potential mechanism for cannabinoid regulation of neuronal firing, but it will obviously be important to confirm that similar mechanisms are also at play in the eyes of mammals,” noted Dr. Ruthazer. “Though technically more challenging, a similar study should now be performed in the mouse retina or even in cultures of human retinal cells.”