Dr. Todd Schlesinger discusses cannabinoids and exosomes, including receptors and regulatory outputs, key discoveries, and anecdotal findings exosomes in dermatologic treatment.
Todd Schlesinger, MD, FAAD, Medical Director, Dermatology & Laser Center of Charleston, Charleston, South Carolina.
“We talked about cannabidiol and its possible uses in dermatology,” said Todd Schlesinger, MD, FAAD, who presented “Novel Ingredients: Exosomes and CBD in Dermatology” at Music City SCALE 2023.
“There are receptors in the body that respond to cannabidiol-type products—the CB1 and CB2 pathways primarily,” he said.
While cannabinoid 1 (CB1) receptors have high expression levels in the central nervous system, CB2 is peripheral and may be found in the skin where the use of topical CBD could affect receptors related to keratinocyte differentiation, sebum production, inflammation, seborrheic dermatitis, psoriasis, and atopic dermatitis, according to Dr. Schlesinger.
Receptors and Regulatory Outputs
“There are different receptors for cannabinoids that can be found in the hair follicles and the sebaceous glands. They oftentimes have regulatory outputs that can change, for example, IL-2 can be increased, which is anti-inflammatory, and TNF-alpha can be decreased, which is, of course, inflammatory.”
Topical cannabinoids can stimulate the release of arachidonic acid as well, said Dr. Schlesinger. They also inhibit COX-1 and COX-2, cyclooxygenase end products, which are found in the skin.
“So there’s lots of different places where they have an effect on the skin. That means that they may have effect on itching, psoriasis, [and] atopic dermatitis, for example.”
According to Dr. Schlesinger, many dermatologic conditions are related to these inflammatory pathways, including allergic contact dermatitis (CB1 and CB2 receptors), lupus (CB1 and CB2 receptors), systemic sclerosis (CB2 receptors), and chronic itching (peroxisome proliferator-activated receptor [PPAR]-alpha).
“But suffice it to say, there are those two groups of receptors—the CB1, which are primarily central, and CB2, which are primarily peripheral, as far as the general receptor pathways go.”
Key Discoveries
The specific binding sites were discovered in the 1980s and CB1 and CB2 in the 1990s, said Dr. Schlesinger. Other receptor discoveries have since followed.
“[The] GPR 55 [receptor] is the one that results in increased IL-12 and endocytic activity and the life of polysaccharide-activated monocytes. So those are immune system functions. So it actually inhibits that receptor. So each one has its own response.
But current research is somewhat limited, he said.
“Right now we’re just doing a topical itch study for CBD. There are others who are looking at rosacea and acne and eczema and atopic dermatitis.”
Notably, CBD is primarily studied as a cosmetic, not a drug, said Dr. Schlesinger.
“So, in reality, everything we’re doing research wise is just right now more informal, looking at its effect on symptoms as opposed to disease states.”
Anecdotal Findings
Anecdotal evidence has shown that CBD can help in reducing the inflammation associated with dermatitis, acne, and rashes, said Dr. Schlesinger.
“Atopic dermatitis can be improved with [CBD] and we’re looking at topical itch right now, but all the evidence is only anecdotal as far as what we’ve done in practice.”
That said, cannabinoids may be effective anti-acne agents, said Dr. Schlesinger.
“They have three main functions.”
They are:
- Lipostatic: Decrease lipo production for acne
- Anti-proliferative: Help to improve keratinocyte function
- Anti-inflammatory/Anti-pathogenic: May help to reduce bacteria content by stimulating the body’s innate immune functions
“So it may be helping in those ways based on just some of the underlying research that has looked at the effects.”
The bottom line with CBD in dermatology is this, said Dr. Schlesinger:
“It’s just more like we’re trying it. We’re seeing if it’s going to have health benefits.”
Examining Exosomes
Exosomes are being produced by multiple companies from multiple sources, said Dr. Schlesinger.
“[Exosomes are] a form of extracellular vesicle. Cells produce mainly three types of extracellular vesicles. They produce exosomes, which are the smallest. They are between 30 and 100 nanometers. They produce micro vesicles, which are larger (100 to 1000 nanometers), and then you have apoptotic bodies, which are 1 to 5 micrometers.”
Exosomes, probably best described as intercellular communication vesicles, contain proteins, micro RNAs, and lipids, said Dr. Schlesinger. All cells produce exosomes to communicate with one another.
“Nobody’s been really good at characterizing what’s in exosomes, but they’ve found ways to harvest them through various processes from various sources. Sources can be plant; they can be animal; they can be human; they can be platelet, for example; they can be adipose tissue; they can be bone marrow; they can be umbilical stem cell, placental—just different tissues.”
Exosomes are primarily harvested from stem cell conditioned media then purified, said Dr. Schlesinger.
“The difference between exosomes and stem cells is that stem cells [are] alive… They can’t be produced in large quantities. They must be very carefully preserved and transported because they’re alive. They produce information. Whereas exosomes are exogenous nanoparticles, which can be sterilized, stored, transported, lyophilized into a powder. They can be found in every body fluid, and they carry information as opposed to producing information. And they may have a wider therapeutic potential. They’re also less immunogenic than stem cells because stem cells have the receptors on the surface that may … create immune responses where exosomes don’t.”
Currently, exosomes are applied to the skin topically, as a cosmetic, and should not be injected, said Dr. Schlesinger.
“Topically, they’re helpful for wound care. Oftentimes, they are being used for post procedure care after procedures such as IPL (intense pulsed light treatments), certain lasers, [and] other treatments that cause skin redness to help reduce the redness.”
Overall, exosomes may have various effects, including to improve collagen production, reduce inflammation, and stimulate better wound healing by acting on various receptors, said Dr. Schlesinger.
- GDF15 regulates inflammation, apoptosis, cell repair, and growth
- TGF-beta3 is an anti-inflammatory protein and important for scar formation
- VEGF is the vascular endothelial growth factor that helps in formation of blood vessels
- IL-10 is an anti-inflammatory cytokine
- GDF11 is an antiaging agent
- TNFR1 is a marker that binds and activates the inflammatory cytokine TNF alpha
“They have certain effects, possibly, depending on what may be in them, and again, characterization can be tough.”
Disclosure: Dr. Schlesinger is a consultant for the Benev company.
