By O’Shaughnessy’s News Service February 24 2014   Bonni Goldstein, MD, flew into San Jose yesterday to address some 120 serious, devoted, desperate, courageous parents on the subject of “CBD and Pediatric Epilepsy.” Goldstein is 40-something and could be Bette Midler’s body double (or vice versa).  The seminar was held at the Embassy Suites hotel in Milpitas, and was organized by Realm of Caring California, a foundation associated with the Stanley Brothers of Colorado. An extract from the Stanleys’ CBD-rich plant provided dramatic seizure relief to a little girl named Charlotte Figi, whose improvement was reported to the world by Dr. Sanjay Gupta on CNN last summer. The strain was dubbed “Charlotte’s Web.” Many of the parents who came to hear Goldstein are on a waiting list to get oil made from Realm of Caring plants being grown by Ray Mirzabegian, who also spoke.

 Goldstein is the medical director of Canna-Centers, a chain of clinics. She had previously given seminars in concert with Realm of Caring in Santa Monica and Irvine. “There’s a lot on the internet that’s opinion,” she said, “I’m here to give you the facts.”  

 Over the course of an hour she explained, thoroughly and clearly, what is known about cannabis as medicine.  She touched all the bases:  China, India, Egypt —thousands of years of documented medical use. Dr. William Brooke O’Shaughnessy in India in 1840, confirming that Cannabis extracts could alleviate symptoms —including seizures— for which Western Medicine had no treatment. The Israeli scientists in the 1960s working out the structure of THC and CBD, and assuming CBD was inactive because it wasn’t psychoactive.

A slide illustrated the similarity of THC, a molecule made by the Cannabis plant, and anandamide, a molecule made in the body that activates the same receptor. We homo sapiens developed receptors so neurons can respond to chemicals made by the body. Plant cannabinoids are coincidentally effective.

  A synthetic cannabinoid, radioactively labelled, revealed where  cannabinoid receptors are concentrated in the brain. Areas of the brain where ECB receptors are concentrated are involved with pain, memory, learning, anxiety, motor coordination, appetite, nausea and vomiting, pleasure and reward. The successful search for endocannabinoids “began the big push into cannabinoid research and therapeutics.” CBD and THC “are natural to your body.” Endocannabinoids are involved in numerous physiological processes; Goldstein listed five that have been identified to date in humans (anandamide, 2-arachidonoylglycerol (2-AG), Noladin ether, virodhamine, and N-arachidonoyldopamine). 

Terpenoids, the essential oils in the plant, give off aromas and have anti-anxiety, anti-inflammatory and many other medicinal effects including,  Flavonoids have anti-inflammatory and anti-oxidant properties. “All these compounds working together create an ‘entourage effect…’ I’m in favor of the whole plant. By pulling things out of it we may be losing some of the synergies. It will be great to do studies comparing whole plant extracts to single compounds.”

 Most of the Cannabis plants in California have been crossed and hybridized. “Sativa” and “Indica” refer to the morphology of the plant. The resinous trichomes make Cannabigerolic Acid. Enzymes determine whether the CBGA will be transformed into CBD or THC. Strains like Charlotte’s Web, ACDC and Cannatonic have been bred to contain high levels of CBD and lower levels of THC.  

The effects of THC and CBD are similar in some ways, opposite in others. “Kind of a yin-yang relationship.” THC can be sedating, CBD can be alerting but if you take larger doses it becomes sedating. CBD does not stimulate appetite. Both have anti-tumor effects. “They work together to enhance each other’s ability.” 

Bonni as Dylan

Explaining a slide showing two neurons: “The pre-synaptic cell is releasing a chemical messenger…” Endocannabinoids are made by the receiving cell and sent back across the synapse. In seizure disorders, the sending cell is overexcited but the receiving cell is not sending back the turn-it-off message. External cannabinoids can say “turn off the message.”  

There is no fatal overdose because there are no receptors in the area of the brain where respiration is controlled…The CB2 receptor mainly in the immune system: spleen, white blood cells, the GI system, the peripheral nervous system, bone, reproductive organs, heart.

“The number of receptors changes in response to environment…There are numerous animal studies and one in children showing that the number of receptors go up (are “up-regulated”) in the disease state. Researchers have found an increase in the number of receptors in the brains of animals that had a lot of seizures. Why? The theory is that the body makes them to try to catch whatever cannabinoids are coming by. ‘Hey, give me more I need more.’ Researchers think there is an endocannabinoid dysregulation with seizure disorders.”

Similarly, in an animal model of Crohn’s diseasean increased number of receptors were found in the gut.  Animals exposed to neuropathic pain and sleep-deprived rates also have an increased number of receptors in their brain. A recent study found an increased number of CB2 receptors found in the white blood cells of children with autism. “It’s almost as if their cells are screaming for more cannabinoids.”  

 “A seizure is a clinical manifestation of the hyper excited neuronal network where the electrical balance underlying the normal activity in the brain is pathologically altered. Excitation predominates over inhibition. The cannabinoids act to suppress the excitation.” Conventional anti-epilepsy drugs augment or enhance the inhibitory process or oppose the excitatory process… Endocannabinoid dysfunction = loss of inhibition = increase excitation  

A study in 2003 (Wallace, M.J., et al. in Journal of Pharmacology and Experimental Therapeutics,  October 2003 ) using a model of epilepsy in rats: plant THC and synthetic THC controlled seizures better than phenytoin and phenobarbitol.   They also found that blocking the ECB receptor increased seizure duration and frequency.  The researchers concluded “The endocannabinoid system plays a critical role in modulating seizure activity in epilepsy”. 

Goldstein’s presentation included an original graphic showing that CBD and the conventional anti-convulsant drugs have some similar mechanisms of action: How CBD may stop seizures

 A small survey in Epilepsy & Behavior (Porter, B. and Jacobsen, C. in Epilepsy & Behavior 29 (2013) 574-577) —19 parents of kids with severe epilepsy reached through a Facebook page. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox–Gastaut syndrome and idiopathic epilepsy.  Average number of anti-epileptic drugs before using CBD: 12. Sixteen of 19 patients reduced seizures using CBD. Two reported complete freedom from seizures. Eight reported greater than 80% reduction. six percent reported 25-50% seizure reduction. Sample small but results very good.Survey Results of patients with seizures using CBD rich Cannabis

“If you try it and it is effective, we do know that there will be fewer side effects.” Side effects: Increased alertness, better sleep. Also drowsiness and fatigue. “But we don’t see on here liver failure, vomiting, ‘child won’t wake up’ and so on…”

CBD also neuroprotective —anti-inflammatory and anti-oxidant properties protect neurons in brain… “They took these poor animals and cut off oxygen and blood flow to their brain for 30 minutes.” Less cell death in animals given CBD.  Alcohol-induced brain damage reduced by CBD.  

The hippocampus is your learning and memory center. One of the most electrically excitable parts of the brain. Affected during seizures. Responsible for new brain-cell growth. CBD may help promote new brain cell growth. “A very important part of its promise.”  (Esposito, et al. Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement.  PLoS ONE 6(12): e28668. doi:10.1371/journal.pone.0028668) 

Research into other cannabinoids. CBDV has anti-seizure effects. One study shows CBD + CBDV = better seizure control.   (Hill, TD et al.  Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism.  British Journal of Pharmacology October 2013)

Warning: the cytochrome p450 enzyme system in the liver that breaks down many medications also metabolizes CBD. Competition might ensue. Watch to see that the other medication levels are not going up or down when giving CBD. Start with a low dose and if you see side effects, contact the doctor. Some children have no problems at all. Some have problems. [Goldstein has had “a small number of patients have lethargy or sedation from low-dose CBD, and a few have had increased number of seizures which I attribute to CBD interfering with the metabolism of the anti-epilepsy drugs the patients are taking.”]

There is a debate on whether to use THC in children.”For me it’s a case-by-case decision. If you’re nervous about THC, you can get CBD that has very low levels of THC.”  For some patients THC does help them control their seizures. “For some children I take care of, THC gives them better sleep at night.  When you use CBD and THC together you can use more THC don’t need to be concerned about small doses of THC because in the face of a high CBD to THC ratio, the CBD will act to dampen down the psychoactivity  The importance of the CBD-to-THC ratio. Example of a ACDC strain:  very low in THC = 0.6 percent— very high in CBD = 18%.  Ratio is CBD divided by THC – in this example it is 18 divided by 0.6 which is 30:1 ratio.  Concentration tells how many milligrams per milliliter the extract contain. 

 Tested medicine has become the norm.  Labs can test for cannabinoid levels and terpenoid levels. Both Charlotte’s Web and ACDC have tested high in the terpenoid Beta Caryophyllene, a very important anti-inflammatory which we want for brains that are having seizures.

GW Pharmaceuticals developed Sativex, a 50-50 CBD-to-THC extract. And now Epidiolex, 25 milligrams of CBD in 1 milliliter, trace amounts of other cannabinoids, and no THC.  Dr. Goldstein on Epidiolex and Sativex

Plants from same strain can have different cannabinoid levels. Plants respond to light, nutrients, growing conditions. Parents have to figure out how much CBD and/or THC the child needs by starting with low-dose CBD-rich oil and taking the time to see what works. “We may see trends when we start looking at the data.”   Goldstein’s staff is analyzing data from her practice. “In another month we’ll have a six-month report.”

 “I encourage people to have a physician on board when they’re weaning off seizure medications. It can be gnarly, there can be withdrawal. We wait till we see that the CBD is working and sometimes that can take a while because we start with a low dose and slowly work up. The current theory is to go real slow and make one change at a time.”

“The Realm of Caring staff who have been working with lots of families over the past two years in Colorado have recommended Benzos are a good one to wean first because of their side effects… Another one to wean is the last drug added. It’s a case-by-case decision. People respond to medication differently.   We don’t want to generalize: ‘this goes first, this goes second.’ Having a neurologist that supports trying this type of treatment is very important.” 

Over a slide of children she takes care of: “It’s really been a rewarding thing to be able to take care of these kids. 

A Word From Our Sponsors 

Dr. Goldstein was introduced by Kevin Reid of the Ghost Group, whose properties include, the leading dispensary locator on the net, and, a news and information service. “The company’s success has allowed us to host special events like this,” said Reid. A crew was on hand to make a video for showing on YouTube. 

Goldstein was followed by Ray Mirzabegian the director of Realm of Caring Foundation California. Many in the audience were on the waiting list for CBD-rich oil from the Charlotte’s Web plants that Mirzabegian and his brothers are growing at three locations in Southern California. “No more than ninety-nine plants per facility,” Mirzabegian explained. “We are doing everything legally.” He gave up a career (instructing opticians) to grow medical cannabis for his daughter Emily, now 10, and others in urgent need. His brothers Alfred, a general contractor, and John, a hair-transplant technician, are also spending 14-15 hours a day growing plants organically for RoC California. 

Read our account of Mirzabegian’s talk here.