Adrenal Function and Cannabis for Pain

"Cannabis is becoming more prevalent," states a recent paper discussing how maternal cannabis use is associated with higher cortisol, anxiety, aggression, and hyperactivity in young children. Another clinical review likens the increased prescription and recommendation of cannabis for pain to the prescription opioid epidemic still wreaking havoc in our society. The recent marketing of cannabis as a benevolent cure-all for anxiety and pain has buried any possible negative outcome in cute products such as CBD gummy bears, cookies, fruit teas, perfumes, and skincare products.The women trying to improve morning sickness are not smoking cigarettes or drinking alcohol, reading articles in publications like High Times, discussing how cannabis has been used to treat "tummy" aches for decades. Even though the American College of Obstetrics and Gynecology warns against using cannabis products during pregnancy, well-known obstetrician Dr. Allison Hill says there isn't any research to prove it causes congenital disabilities. Like the paper above, the study shows it can cause behavioral problems, which she says is difficult to interpret. Elizabeth Bachner, midwife and owner of an LA Birthing center claimed the fact that women are warned away from cannabis during pregnancy is a "smear campaign." High progesterone causes morning sickness to ensure the body doesn't reject the fetus. A high-fat carnivore diet can often mitigate this.

I've had three children. I understand how it feels. Eating anything is sometimes challenging during the first trimester. There are definite ways around this. Cannabis isn't the answer. Cannabis is a powerful drug. The fact that it has been used for thousands of years as a potent drug does not mean it doesn't have side effects. Most research papers into the sudden ubiquitousness of cannabis as a treatment for anxiety start with this —cannabis has been used for thousands of years. Pregnant women using cannabis in California have doubled since 2009. The study linking maternal cannabis use to children's behavioral problems has been around since 1978. I was 11 in 1974 when I found out my mother and stepfather smoked marijuana at a party. I knew it was illegal and worried the police could take them away. My fear drove my stepfather to leave three paperbacks explaining that, well, people used cannabis for thousands of years.

Cannabis is a drug that will lower the natural stress response. A research paper from 2015 illustrated how exogenous cannabinoids decreased the adrenaline response in rabbits being zapped with electricity. Hence, it will reduce how you react to pain but not lessen the damage the pain causes. This works until the user becomes chronic—like any anxiolytic, be they benzodiazepines or antidepressants—they work by hacking the adrenal stress response. Biohacking is very popular now. It makes you feel like if you can lift this lever here and lower that lever there, you can change the outcome of your physiology. This concept makes me think of the old "It's not nice to mess with mother nature" ad for yucky margarine, but I think the point is essential. Health, to me, means optimizing your body's ability to thrive. If you are in pain and you cannot lessen it by other means, that may make sense, but you have to be conscious of the drawbacks.

Raphael Mechoulam isolated the phytochemical THC in 1964, almost three decades before Lumir Hanus and William Anthony Devane identified the endocannabinoid system and isolated the endocannabinoid in the human brain in 1992. They named it anandamide, the Sanskrit word for bliss. They called the receptor system the endocannabinoid system because THC attaches to it. But because it connects to it does not mean we need THC, just as the fact that opiates attach to opiate receptors does not mean we need opiates. Unfortunately, as the name implies happiness, the marketing of cannabis as a treatment has hoodwinked the public into thinking it does indeed give bliss, to the extent that it is provided at weddings like champagne to create a mood. It does not. It distracts you from listening to your body's signals that something is wrong.

The endocannabinoid system (ECS) modulates how you react to physiological stress, inflammation, pain, and even memory. The endocannabinoid receptors CB1 and CB2 are found in the nervous and immune systems. CB1 mediates neurotransmitter release, and CB2 modulates the release of cytokines. It's not sure if CB2 inhibits or promotes an immune response. Promoting an immune response could create autoimmunity, which would get out of hand in response to inflammation. The receptors modulate the stress response in the heart, digestion, liver, immune system, muscles, bones, reproductive system, and skin—the immune response in all tissues since all tissues respond to immune stress. CB1 receptors are predominant in the central nervous system—the brain, the hypothalamus, and many peripheral tissues. They are found in neurons that respond to GABA, glutamate, serotonin, adrenaline, and dopamine.

Research has demonstrated that activating the CB1 receptors in brain mitochondria decreases cellular respiration and causes impaired memory formation. The main effect of endocannabinoid signaling is to modulate how these neurons respond to neurotransmitters. The endocannabinoid system keeps us calm in response to danger or pain to promote survival and restore homeostasis. If the threat is high enough to activate the system, it will buffer the stress response. Buffering the stress response means that if there is danger, you get scared but not too scared that you freeze, instead running like hell.

Cortisol directs this system. Anandamide, what Linus Hamur named bliss, is an endogenous endocannabinoid synthesized in response to acute stress to inhibit the HPA axis and restore homeostasis. It regulates the feedback loop by increasing levels of endocannabinoids. Since glutamate is the excitatory neurotransmitter, cortisol suppresses glutamate excess so you don't freeze in fear. Cortisol uses endocannabinoids to temper the HPA axis stress response. All those neurotransmitters that cortisol directs to release—norepinephrine to the heart to make it beat fast, sugar to the muscles to give you the energy to run, etc., will be tempered so you don't have a panic attack and stand there riveted to the spot. HPA axis suppression leads to an altered stress response and an inadequate or exaggerated defense against infections, which is autoimmunity.

When stress is chronic, this whole system is disrupted and dysregulated. Under repeated or constant stress, too much cortisol is secreted. Down-regulated cortisol receptors blunt a healthy stress response. Cortisol falls on deaf ears as more endocannabinoid receptors become occupied. This down-regulation of the natural stress response reduces Amandamine synthesis, resulting in more significant GABA inhibition and down-regulation of CB1 receptors. The suppression of the release of GABA increases the excitatory effects of norepinephrine. This situation leads to more stress and increased anxiety, similar to post-traumatic stress syndrome.

Cannabis consumption, in any form, increases cortisol levels. Even chronic micro-dosing of cannabis leads to a blunted HPA axis response to stress. The hypothalamus-pituitary-adrenal stress response is a beautiful and complicated symphony of negative feedback loops that becomes cacophonous if any part plays the wrong tune. In response to acute stress or any drug that affects this response, the HPA axis releases corticotropin-releasing hormone (CRH) from the hypothalamus, which promotes the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland, ultimately resulting in cortisol secretion from the adrenals.

Those who use cannabis may feel less stress at the same time the cortisol is spiking. These people will also avoid stress—they become emotionally disconnected. The constant increase of cortisol will cause the hypothalamus to reduce the secretion of ACTH because cortisol is catabolic. That's why chronic stress is so damaging. It's like diabetes of the sympathetic nervous system. The reduced hypothalamic response means more cannabis is needed to "feel" less. The blunted response to stress causes anxiety and depression. The same dysregulation causes those who use cannabis to relieve pain to feel the same pain more acutely. This is the problem I see with cannabis and its derivatives, even though humans have used it for thousands of years. Other drugs have been used for thousands of years—peyote, opium, etc., usually by a specific member of the tribe who was responsible for "seeing things." That medicine

person didn't have to do regular work in the tribe. They usually didn't have children. I think of it more as a sacrifice— like in the Dune books— where the mind and body of those who regularly took the spice to see across galaxies and into the future became deformed. It's not a great idea forregular people. It should be legal and should be treated as a medicine, not a cure-all.