How the brain protects itself from the negative effects of CBD
Hashish, generally often called marijuana, has an extended historical past of medicinal and leisure use. This plant comprises over 100 substances with bioactive properties known as cannabinoids, from which probably the most well-known are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Whereas THC is a psychoactive molecule that alters mind operate, producing adjustments in notion, temper, cognition, or conduct, CBD doesn’t.
Our physique additionally produces its personal cannabinoids — known as endocannabinoids — and has a complete endocannabinoid system which performs an vital function in regulating varied physiological processes, reminiscent of relieving ache and controlling urge for food, stress, and irritation. Exterior cannabinoids, like CBD, work together with our endogenous endocannabinoid system, modifying physiological operate.
How does CBD have an effect on mind well being?
Making the most of hashish’ properties, it has been used medicinally to deal with totally different circumstances, together with some neurologic issues. The primary CBD-based medication was authorized by the FDA in 2018 to deal with sure forms of epilepsy.
Regardless of its advantages, CBD could cause delicate negative effects, reminiscent of dizziness and drowsiness, with some research suggesting it may be dangerous to the mind, inflicting neuron demise. Nonetheless, there are extra cell varieties than simply neurons within the mind. Astrocytes, for one, are a kind of supportive cell within the nervous system that protects neurons from hurt.
To raised perceive how CBD impacts neuron well being within the mind and the dangers related to consumption, a bunch of scientists from the Korea Superior Institute of Science & Know-how (KAIST) in Daejeon, South Korea established a singular experimental system to discover how astrocytes would possibly defend neurons from CBD neurotoxicity. Their outcomes have been just lately revealed in an article in Superior Biology.
“We beforehand discovered that top doses of CBD may hurt neurons,” mentioned Insung Choi, professor of Chemistry and of Bio and Mind Engineering, and Director of the Middle for Cell-Encapsulation Analysis within the KAIST. “Nonetheless, this examine has revealed that astrocytes can really mitigate this dangerous impact. This implies there’s much less purpose to be involved about CBD inflicting injury to neurons.”
The findings of this examine may doubtlessly pave the best way for the event of extra CBD-based drugs for neurological circumstances, assuaging issues about adversarial results.
A useful mobile “sandwich”
Within the lab, cells are usually grown or cultured in flat plates. When a couple of sort of cell is cultured collectively in a co-culture, each cell is blended collectively on the identical plate, offering a platform that permits them to work together bodily with one another to check their behaviors.
Choi and the staff wished to find out if astrocytes have been releasing molecules which may defend neurons towards the results of CBD. Whereas the staff wanted to check how each cell varieties work together in such a setting, to keep away from pointless interference, they wanted to develop every cell sort independently. To do that, they needed to design a totally new co-culture methodology.
Astrocytes and neurons have been grown independently in small, round glasses situated on the backside of tradition plates. The glasses the place astrocytes have been grown contained spacers on their borders such that when positioned face-to-face over the plates with neurons, this helped keep away from bodily contact. The staff check with this association as a “sandwich” co-culture.
“The sandwich format permits us to check the results of drugs launched by each astrocytes and neurons in a confined space,” mentioned Choi. “This implies we are able to examine the impression of soluble compounds with out direct contact between the cells.”
As a part of the management group, the scientists employed a neuron/neuron sandwich association, and upon remedy with CBD, they noticed neuron cell demise in a concentration-dependent method. Nonetheless, when CBD was utilized to a neuron/astrocyte sandwich configuration, neurotoxicity was not noticed at low CBD concentrations (15 μm).
Choi and the staff additionally discovered that at a excessive CBD dose (30 μm), 10% of neurons within the co-culture died, whereas within the neuron/neuron sandwich, nearly 50% of the neurons died. The researchers counsel that the presence of astrocytes act as a protecting mechanism, attenuating the detrimental impression of CBD on the neurons.
To research how CBD kills neurons, the scientists carried out a method known as calcium imaging that measures calcium concentrations contained in the cell — an indicator of cell demise or apoptosis.
Choi and the staff noticed that neurons handled with CBD had excessive intracellular calcium focus, however when astrocytes have been a part of the sandwich, the share of neurons that confirmed excessive calcium focus was far decrease. The authors speculate that the astrocytes rescued neurons from CBD toxicity and demise by regulating calcium mechanisms contained in the cells.
In addition to finding out neuronal viability, Choi and the staff additionally investigated the cells’ structural and morphological adjustments. A neuron consists of a cell physique and skinny, elongated projections that reach from it known as neurites. When uncovered to CBD, the neuron/neuron sandwich confirmed shorter neurites, indicating points with cell progress, and “demise cues” known as apoptotic our bodies, whereas the neurons within the co-culture with astrocytes didn’t present indicators of harm.
“We noticed that the liquid by which astrocytes have been grown, together with CBD, helps neurons develop sooner to some extent,” mentioned Choi. “This implies the potential of a mixture of CBD and the substances secreted by astrocytes in response to CBD as a brand new therapeutic method for mind accidents.”
A scientific context for CBD
This analysis carries vital implications for CBD as a possible therapeutic agent for neurological issues by offering essential data that might support within the design and optimization of CBD-based therapies.
Nonetheless, neurons from totally different mind constructions may react in several methods. Whereas Choi’s group carried out their experiments with mouse neurons from an space within the mind concerned in reminiscence, extra research might be wanted to grasp CBD’s results in different areas.
“We selected hippocampal neurons as a result of they play an important function in reminiscence and function a doubtlessly appropriate mannequin cell for finding out Alzheimer’s illness,” mentioned Choi. “Nonetheless, as a part of our analysis plan, we additionally intend to check the results of CBD on cortical neurons and neural stem cells.”
Along with the therapeutic properties of hashish compounds, leisure use can also be turning into extra prevalent. Whereas Choi’s analysis was based mostly solely on the scientific functions of CBD, additional investigation is required to completely perceive the results of hashish on the nervous system.
“Our analysis is targeted solely on the medicinal utility of CBD and isn’t related to the leisure use of Hemp or Hashish,” Choi mentioned. “We particularly investigated the neurotoxicity of ‘pure’ CBD and its neuralization by astrocytes on the cell-culture degree.
“When contemplating CBD for medicinal functions, it’s essential to make sure its purity by means of rigorous high quality management measures,” he continued. “It must be famous that Hemp or Hashish merchandise meant for leisure use comprise a large number of compounds, together with cannabinoids like psychoactive THC, varied terpenes, and even unidentified compounds. The interactions and results of those compounds within the physique could be intricate and interrelated.”
Reference: Jungnam Kim, et. al., Neutralization of Cannabidiol Neurotoxicity in Neuron-Astrocyte Sandwich Coculture, Superior Biology (2023). DOI: adbi.202300090
