Five years ago, my resident and I presented a poster at a Boston-based biotech meeting called BIO 2008. It was fairly quiet around the poster exhibit that day, with only a few people stopping to ask questions. At the poster next to us was an elderly scientist who, like us, was not receiving much attention. I said to my resident, "Why don’t you pop over to see what his poster is about? I’ll hold the fort until you get back.” So off she went and I saw her discussing the poster with him in some detail. She returned a few minutes later with some printed materials and explained what his poster was about. "It’s about treatment of seizures in mice using Huperzine,” she reported. "His name is Dr. Schachter and he’s from Beth Israel Hospital.” "Not Steve Schachter?” "Yes, that him,” she replied, pointing to his name on the printed sheets. "Oh my gosh, I know him from years back,” I said and went over to speak with him. He recognized me immediately so we chatted and caught up. "So what’s this Huperzine stuff?” I asked. "Oh, it’s an herbal extract that we have had purified. It’s one of the best anticonvulsants I have tested,” he replied. Schachter went on to explain that in a seizuring mouse model that he had employed, Huperzine’s dose-response curve was pretty much a straight line to zero. When Dr. Schachter says anything, I listen closely. Full professor at Harvard, editor of the journal Epilepsy and Behavior, and driving force behind the website Epilepsy.Com, his credentials are impeccable. Needless to say, I wanted to know how he thought Huperzine worked. He informed me it was an anticholinesterase inhibitor (AChI) and that was the reason for its efficacy in treating seizures and its purported value in treating Alzheimer’s disease and other cognitive impairment. He also mentioned that Huperzine is an NMDA receptor antagonist, blocking glutamate, the main excitatory neurotransmitter in the central nervous system. I was interested in that because we had shown that NMDA blocking drugs are effective in treating compulsive disorders in various species of animals. Back at the vet school, I looked up some facts about Huperzine. First, I found out that Huperzine is an alkaloid extract of the Chinese club moss, whose botanical name is Huperzia serrata. Some Info Huperzine is available over the counter and at most health product stores in capsule form. Capsules range from 50-200 micrograms (mcg) in strength. Based on extrapolations from human use, I came up with a dosage of Huperzine that was between 50 and 400 mcg twice daily. I learned that Huperzine is well tolerated in humans but was very cautious with the first veterinary patients (dogs) that I treated, starting out at the low end of that dose scale. Later I was told by a company thinking of marketing Huperzine that the dose at which adverse effects first appear in dogs is 300 mcg per kilogram of body weight. That side effect was salivation, undoubtedly a result of the AChI effect. This extra knowledge of Huperzine’s safety gave me more courage later on to treat dogs with larger doses and I have so far tried doses of up to 400 mcg total dose BID for middle-sized dogs. When you think about it, that is only slightly higher that the "per kilogram” dose before adverse effects occur. In other words, it is quite safe. Focal Seizures One of the first patients we treated was Bernie, a Bernese Mountain dog. Bernie exhibited bizarre episodic star gazing, fly snapping, air licking, chewing and lip smacking. In addition, he showed some fearful behavior, for example, running and bolting from one area of the room to another during these episodes. Thinking that the behavior may have resulted from complex partial seizures, we asked our neurologist to perform an EEG examination under light sedation. Bernie’s EEG showed sharp waves and a spike-and-wave complex on the left side of his brain. The diagnosis of focal seizure was made by the neurologist and anticonvulsant treatment was called for. I elected to use Huperzine at the conservatively low dose 100 mcg and 50 mcg, a.m. and p.m. respectively. This regimen kept Bernie relatively seizure-free for six months, but there was a breakthrough at six months when the local vet prescribed Tramadol for Bernie’s concurrent arthritis pain. Updating an Opinion Knowing what I know now, I would have increased Bernie’s Huperzine dose, but I was new at this at the time and elected to switch to phenobarbital (which also worked). Next, my new resident, Dr. Niwako Ogata, and I started to prescribe Huperzine for cases of canine compulsive disorder (CCD) and Dr. Ogata kept a detailed log of how the dogs fared. Dog after dog did well, with improvement for conditions like tail-chasing, shadow-chasing and flank sucking responding by 40-90 percent, according to owner ratings. Only one dog of 20 or so did not respond at all to this treatment. One good thing about adding an NMDA blocker to existing treatment with a marginally effective serotonin reuptake inhibitor is that SSRIs (fluoxetine, at least) and NMDA antagonists (like memantine) are synergistic where it comes to treating compulsive disorders. It’s a case of 1 + 1 = 3. We have shown that in mice and it has also been shown in humans and is our clinical impression. Is It Useful? All in all, I would say that Huperzine is a useful addition to a vet’s pharmacological armamentarium. It is both effective and safe for a variety of behavioral and medical conditions, ranging from compulsive disorders (alone or as an augmentation therapy), to canine cognitive dysfunction and seizure conditions. I suppose it’s hardly surprising that some herbal treatments might work and offer advantages over conventional treatment. But beware, not all herbal treatments work, not all are safe, and not many are properly controlled for quantity or quality. Approved medications are more trustworthy in these respects and often more convenient. Who wouldn’t rather take a tablet or capsule than chew on the likes of poppy leaves or willow bark? But then again, it is said (by whom I am not sure) that many of the most useful medications we currently have available are derived from less than 1 percent known rain forest or other flota. That leaves a lot of room for future improvisation and we can probably learn quite a lot from close inspection of past empirical botanical applications. An author and researcher, Dr. Dodman is a professor at Cummings School of Veterinary Medicine at Tufts University in North Grafton, Mass., and is founder of Tufts’ Animal Behavior Clinic.
