San Francisco Chronicle

Calming anxiety,

- By Dr. Tracy E. Foose

It’s time to cut the dogma on both sides and take a practical approach to cannabis.

And although marijuana is getting commercial­ized at the state level, illegality under federal law still obstructs U.S. research into its effects on the brain and body. From a scientific standpoint, this means our understand­ing of cannabis remains hazy. Pun intended.

Anxiety relief is an often-cited motive for using cannabis, and so, because I specialize in treating anxiety disorders, I try to stay current on cannabis research.

I don’t recommend cannabis, but when patients report using marijuana to try to manage anxiety, there’s a frank conversati­on we need to have about potential risks and benefits. Here’s what I wish everyone, or certainly everyone who is anxious, understood about using cannabis for anxiety:

A number of distinct compounds play a role in cannabis’ effects. Some increase appetite, some reduce inflammati­on, some even show promise for fighting cancer. Of these compounds, THC (tetrahydro­cannabinol) and CBD (cannabidio­l) have the greatest name recognitio­n, in part because they’re often listed by milligram on packaging of cannabis commercial­ly marketed for use. These “cannabinoi­ds” affect our state of mind and sense of well-being.

In our brain, cannabinoi­ds can bind to a receptor known as cannabinoi­d receptor type 1 (CB1). Cloning this receptor for the first time in 1990 allowed neuroscien­tists to discover which natural brain compounds (endocannab­inoids) bind to CB1. After all, these receptors have a purpose long predating our desire to eat, smoke or vape a sticky plant we found in the Asian

Dr. Tracy E. Foose of Mill Valley specialize­s in treating people with anxiety.

steppes.

Since their discovery, we’ve learned that endocannab­inoids play a role in regulating everything from sleep and appetite to the joyful bliss of a runner’s high. They do so by modifying the release of other neurotrans­mitters that have a more direct impact on mood, energy and anxiety.

At their naturally occurring dosing and distributi­on in the brain, endocannab­inoids help maintain homeostasi­s (the brain’s baseline state) via what’s known as retrograde signaling (feedback loops that travel backward through a neural circuit to reset the system). Their regulating activity at CB1 receptors influences both excitatory and inhibitory signaling in the brain.

Think of (endocannab­inoids) as being like great emcees: They promote the party, approve the playlist, get everyone on the dance floor and wind them all down at the end of the night.

CB1 receptors are found in high numbers in areas of the brain that appraise threats and manage our fear response. Binding of endocannab­inoids appears to decrease the brain’s reactivity to threat, which helps explain why many people experience the cannabinoi­ds as anxiety relieving.

But with regular use of cannabis, your number of CB1 receptors decreases — that is, they are downregula­ted, pulled off the surface of the neuron and taken out of play. So although the compounds in cannabis can induce a feeling of calm and well-being by binding to CB1, they leave areas of the brain less sensitive to its own natural endocannab­inoids. With cessation of cannabis use, CB1 receptors begin to recover their normal numbers within days.

Here’s where it gets interestin­g: THC demonstrat­es a funky biphasic dose effect. This means that at low doses it does one thing, and at higher doses it does the opposite. This is not really news to anyone who has ever tried marijuana, as it’s common knowledge that a little makes you mellow, but a little more can give you “the fear.” What’s surprising is how narrow the dose window appears to be between happy and anxious — especially for the new or infrequent user. A significan­t proportion of patients with newonset panic attacks report cannabis as the trigger and worry that they’ve caused lasting damage. (The answer is no, but when your brain has an intense scare, it tends to revisit the experience again and again, perhaps to assess the actual threat.)

To examine the biphasic dose window in more detail, a recent study at the University of Chicago looked at people who had used cannabis before but were not regular users. It showed that 7.5 mg of THC induced a mild elevation of mood and sense of well-being, while 12.5 mg of THC made subjects anxious.

Edible varieties of cannabis are often sold in 10-mg doses of THC. Take for example, the iconic pot gummy bear. Eat all but the feet of one gummy and compare the experience to eating a whole gummy plus the head of another. That’s about 7.5 mg of THC compared with 12.5 mg.

So for the infrequent cannabis user, the line between fun and fret comes down to fragments of a gummy. With regular use of cannabis, this window appears to widen: Regular users have less anxiety and

paranoia associated with THC ingestion than infrequent users.

But that’s not the whole story. CBD appears to combat the anxiety-inducing impact of THC. Depending on what kinds of signaling activity are going on, what your own endocannab­inoids are up to (factors controlled by your mood and physical settings), the arrival of THC and CBD on the scene has widely varying impacts.

To complicate things further, everything from age, amount of body fat and genetics influences how cannabinoi­ds compete with endocannab­inoids for binding to the CB1 receptors in our brain. The adolescent brain, for example, is far more susceptibl­e to the risk of developing transient auditory and visual perception­s and odd thoughts with exposure to cannabis — teens are wired so very differentl­y from adults. More than one parent of an adolescent suffering from anxiety has asked me what I think of their sharing marijuana with their anxious child, and my answer is an emphatic “Under no circumstan­ces.”

To add a final layer of complexity: Factors like growth conditions, preparatio­n and time of harvest will affect the chemical compositio­n of any plant product, cannabis included. THC degrades as it ages to a compound called CBN (cannabinol) with an entirely different profile of action from that found in a fresh bud of cannabis — one that’s associated with lethargy and headache.

We live in a culture of more is more. But apply this maxim to the use of cannabis for anxiety and you risk overshooti­ng the mark with a dose that makes your skin crawl or gets in the way of your own endocannab­inoids.

You know your brain better than anyone else. If you try cannabis, do so armed with knowledge and intent. Know what you’re doing when you take the extra puff, eat the other gummy bear — or all the gummy bears, for that matter. It’s fine to embrace the cliches. Stare at the fire for four hours. Make a dinner of Cheetos. Write texts composed entirely of emojis. Just don’t confuse mellow with immobilize­d.

Dr. Tracy E. Foose specialize­s in the treatment of anxiety disorders. She practices psychiatry in Mill Valley and is an associate professor of psychiatry at the University of California, San Francisco School of Medicine.

 ?? Carlos Avila Gonzalez / The Chronicle ??
Carlos Avila Gonzalez / The Chronicle
 ??  ?? For the infrequent cannabis user, the line between fun and fret comes down to fragments of a gummy.
For the infrequent cannabis user, the line between fun and fret comes down to fragments of a gummy.

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