1 00:00:01,000 --> 00:00:01,830 Welcome, everybody. 2 00:00:02,009 --> 00:00:03,110 It's so nice to see so many 3 00:00:03,110 --> 00:00:03,949 of you here this morning. 4 00:00:04,610 --> 00:00:05,920 So I'm gonna be talking about GABA. 5 00:00:06,660 --> 00:00:07,830 What's GABA got to do with it? 6 00:00:08,809 --> 00:00:09,029 R. 7 00:00:09,030 --> 00:00:09,099 I. 8 00:00:09,099 --> 00:00:09,449 P. 9 00:00:10,390 --> 00:00:11,190 My name is Dr Scott. 10 00:00:11,190 --> 00:00:11,550 Sure. 11 00:00:11,579 --> 00:00:13,460 I'm the chief operating officer of Health 12 00:00:13,460 --> 00:00:14,790 Optimization, Medicine and Practice. 13 00:00:15,250 --> 00:00:16,840 Our nonprofit organization training 14 00:00:16,840 --> 00:00:19,010 doctors like you and practitioners 15 00:00:19,010 --> 00:00:20,850 like you how to optimize health rather 16 00:00:20,850 --> 00:00:21,974 than treat disease and treatment. 17 00:00:22,535 --> 00:00:24,735 I have a lot of fun with this talk. 18 00:00:24,755 --> 00:00:27,045 I've, this is something that actually Dr. 19 00:00:27,045 --> 00:00:28,585 Ted and I, but mostly Dr. 20 00:00:28,585 --> 00:00:31,385 Ted developed as a strategy for 21 00:00:31,405 --> 00:00:33,915 our overall understanding that 22 00:00:34,715 --> 00:00:36,625 nobody remembers the most important 23 00:00:36,625 --> 00:00:39,005 neurotransmitter in our opinion, GABA. 24 00:00:39,315 --> 00:00:40,985 Everybody remembers serotonin 25 00:00:40,985 --> 00:00:42,825 and dopamine and norepinephrine. 26 00:00:42,835 --> 00:00:43,945 These, these are the fancy ones. 27 00:00:43,945 --> 00:00:45,185 Everybody knows about these, but 28 00:00:45,185 --> 00:00:47,645 everybody forgets about GABA. 29 00:00:47,645 --> 00:00:48,595 So this is going to be a talk 30 00:00:48,595 --> 00:00:50,165 on how GABA is made, what GABA 31 00:00:50,175 --> 00:00:51,735 is and why we should care. 32 00:00:51,815 --> 00:00:53,385 Let's talk about top 33 00:00:53,385 --> 00:00:55,615 symptoms of GABA deficiency. 34 00:00:56,055 --> 00:00:57,855 So if you have a clinical practice, 35 00:00:57,875 --> 00:00:59,405 you probably have some of your 36 00:00:59,405 --> 00:01:00,495 patients with these symptoms. 37 00:01:01,045 --> 00:01:04,795 Anxiety, fear, depression, a short temper, 38 00:01:04,855 --> 00:01:07,695 phobias, impulsiveness, disorganization, 39 00:01:08,115 --> 00:01:10,005 addictions, schizophrenia, 40 00:01:10,005 --> 00:01:11,365 obsessive compulsive disorder. 41 00:01:11,365 --> 00:01:12,675 Any of your patients have any of these? 42 00:01:12,675 --> 00:01:13,485 Probably, right? 43 00:01:13,745 --> 00:01:14,625 But you're not thinking about 44 00:01:14,625 --> 00:01:15,935 GABA deficiency most of the time. 45 00:01:16,635 --> 00:01:18,075 And then systemic symptoms, these are 46 00:01:18,075 --> 00:01:19,655 also associated with GABA deficiency. 47 00:01:20,065 --> 00:01:22,585 IBS, diarrhea, high blood pressure, 48 00:01:22,605 --> 00:01:24,735 tinnitus, chronic pain, migraines, 49 00:01:24,745 --> 00:01:27,565 allergies, frequent urination, flushing, 50 00:01:27,575 --> 00:01:29,835 sweating, salt cravings, muscle tension. 51 00:01:30,185 --> 00:01:32,650 So all of these, could potentially 52 00:01:32,660 --> 00:01:34,550 be showing you that your patients and 53 00:01:34,550 --> 00:01:36,620 clients may have a GABA deficiency. 54 00:01:37,060 --> 00:01:38,180 It's not the first thing on many 55 00:01:38,180 --> 00:01:39,610 of our radars, of course, but maybe 56 00:01:39,610 --> 00:01:41,380 it should be part of that initial 57 00:01:41,940 --> 00:01:43,510 understanding of what might be going on. 58 00:01:44,310 --> 00:01:48,030 GABA is really important, and now even 59 00:01:48,030 --> 00:01:50,700 the drug industries are getting the idea. 60 00:01:50,730 --> 00:01:51,980 So this is the first drug 61 00:01:52,380 --> 00:01:53,770 Approved just recently. 62 00:01:53,830 --> 00:01:55,010 This is a New York Times article. 63 00:01:55,340 --> 00:01:57,040 The first pill for postpartum depression. 64 00:01:57,710 --> 00:01:59,690 And it's called, Zuranolone, 65 00:01:59,710 --> 00:02:00,700 I think is how you say it. 66 00:02:01,060 --> 00:02:03,070 And it is a positive allosteric 67 00:02:03,100 --> 00:02:04,490 modulator of the GABA receptor. 68 00:02:04,490 --> 00:02:05,470 We'll talk about what that is. 69 00:02:05,860 --> 00:02:06,570 But it's supposed to be 70 00:02:06,570 --> 00:02:08,050 used for the first 14 days. 71 00:02:08,300 --> 00:02:09,070 Only for two weeks. 72 00:02:09,595 --> 00:02:10,955 Supposedly, while you're taking another 73 00:02:10,955 --> 00:02:12,715 drug like an SSRI for that to work, 74 00:02:12,715 --> 00:02:14,325 but these work right away because 75 00:02:14,325 --> 00:02:15,355 it's affecting the GABA receptors s 76 00:02:15,595 --> 00:02:18,175 directly and improving depression almost 77 00:02:18,215 --> 00:02:19,925 immediately, too, which is pretty awesome. 78 00:02:19,985 --> 00:02:21,285 You don't have to go directly to drugs, of 79 00:02:21,285 --> 00:02:22,695 course, but sometimes they're necessary. 80 00:02:23,095 --> 00:02:24,295 So, let's talk about GABA synthesis. 81 00:02:24,355 --> 00:02:26,165 GABA is only made in the brain. 82 00:02:26,315 --> 00:02:28,295 Okay, you have to have glutamine, 83 00:02:28,425 --> 00:02:29,775 which is an amino acid, it's 84 00:02:29,925 --> 00:02:31,255 converted into glutamate. 85 00:02:32,025 --> 00:02:32,695 in the brain. 86 00:02:32,925 --> 00:02:34,155 And then glutamate is our 87 00:02:34,155 --> 00:02:35,805 excitatory neurotransmitter. 88 00:02:35,805 --> 00:02:37,815 And you have GABA, which is our 89 00:02:37,815 --> 00:02:39,355 inhibitory neurotransmitter. 90 00:02:39,755 --> 00:02:41,285 So 20 percent of the brain's 91 00:02:41,285 --> 00:02:43,385 neurotransmission is actually GABA. 92 00:02:43,385 --> 00:02:44,335 So it's a huge amount. 93 00:02:44,635 --> 00:02:46,215 And glutamate in GABA combined 94 00:02:46,215 --> 00:02:47,575 is about 80 percent actually. 95 00:02:47,575 --> 00:02:49,715 So it's the combination of the two is the 96 00:02:49,715 --> 00:02:52,305 majority of your neurotransmitter system. 97 00:02:52,725 --> 00:02:55,565 And to make glutamine into GABA, you need. 98 00:02:56,250 --> 00:02:57,360 You need this enzyme called 99 00:02:57,360 --> 00:02:58,230 glutamine synthesase. 100 00:02:58,550 --> 00:03:00,900 And then from glutamate to GABA itself, 101 00:03:01,030 --> 00:03:02,250 you have to convert this, you need 102 00:03:02,250 --> 00:03:04,220 vitamin B6, and you need magnesium. 103 00:03:04,230 --> 00:03:06,180 So you need cofactors along the 104 00:03:06,180 --> 00:03:08,280 way to make this conversion happen. 105 00:03:08,490 --> 00:03:09,420 Some people are really great 106 00:03:09,420 --> 00:03:11,580 at converting GABA into GABA. 107 00:03:11,580 --> 00:03:12,820 Some people are not very good at it. 108 00:03:13,110 --> 00:03:14,210 And a lot of times it's related to these 109 00:03:14,210 --> 00:03:15,720 cofactors, but there's other reasons, too. 110 00:03:16,510 --> 00:03:18,070 And see, here are some of those reasons. 111 00:03:18,080 --> 00:03:20,395 So, If you have a high copper level 112 00:03:20,395 --> 00:03:21,445 and a low zinc level, you're not 113 00:03:21,445 --> 00:03:23,325 going to be able to actually have the 114 00:03:23,325 --> 00:03:24,795 GABA receptor work as effectively. 115 00:03:25,275 --> 00:03:27,555 If you're vitamin B6 deficient, you're 116 00:03:27,565 --> 00:03:29,245 also not going to convert well from 117 00:03:29,415 --> 00:03:31,095 glutamate to GABA, as I mentioned. 118 00:03:31,305 --> 00:03:32,645 If you have chronic stress, if you 119 00:03:32,645 --> 00:03:34,135 have chronic hypercortisolemia, if 120 00:03:34,135 --> 00:03:35,545 you're always stressed, you're going 121 00:03:35,545 --> 00:03:37,445 to deplete your GABA system, and then 122 00:03:37,445 --> 00:03:39,115 your GABA levels are going to go down. 123 00:03:39,925 --> 00:03:41,735 If you're magnesium deficient, and 124 00:03:41,735 --> 00:03:43,095 most of our clients and patients 125 00:03:43,115 --> 00:03:44,345 are magnesium deficient, they're 126 00:03:44,345 --> 00:03:45,495 not going to convert well either. 127 00:03:46,235 --> 00:03:47,315 If you have infection, this 128 00:03:47,315 --> 00:03:48,785 is going to stress the system 129 00:03:48,785 --> 00:03:50,165 and also decrease GABA levels. 130 00:03:50,675 --> 00:03:54,035 Now, GABA supplementation may help your 131 00:03:54,035 --> 00:03:55,595 GABA levels, but actually under most 132 00:03:55,595 --> 00:03:57,755 circumstances it's not going to because 133 00:03:57,760 --> 00:04:00,100 GABA itself is a big molecule and doesn't 134 00:04:00,100 --> 00:04:01,420 go across the blood-brain barrier. 135 00:04:01,420 --> 00:04:02,890 Under , certain circumstances, it 136 00:04:02,890 --> 00:04:04,210 may, and we'll talk about that. 137 00:04:04,780 --> 00:04:06,550 And then probiotics can also help with 138 00:04:06,550 --> 00:04:07,840 this conversion, help with this enzyme. 139 00:04:08,510 --> 00:04:09,940 So, you can actually measure, and 140 00:04:09,990 --> 00:04:11,420 you saw some of these slides with Dr. 141 00:04:11,420 --> 00:04:12,300 Ted, you can actually measure 142 00:04:12,300 --> 00:04:14,460 people's vitamin B6 level, and if 143 00:04:14,770 --> 00:04:16,620 it's low, it's very likely they're not 144 00:04:16,620 --> 00:04:18,130 converting well from glutamate to GABA. 145 00:04:18,170 --> 00:04:19,030 So this is something to be thinking 146 00:04:19,040 --> 00:04:20,630 about, and this is why we do 147 00:04:20,640 --> 00:04:22,760 metabolomics testing as well. 148 00:04:24,290 --> 00:04:25,540 You can check their magnesium level. 149 00:04:25,940 --> 00:04:27,620 In this patient, in this client, it 150 00:04:27,620 --> 00:04:28,900 was a normal magnesium level, this is 151 00:04:28,900 --> 00:04:30,590 red blood cell magnesium, but a lot 152 00:04:30,590 --> 00:04:31,710 of our clients, it's going to be low. 153 00:04:32,170 --> 00:04:33,650 So if you have a low magnesium 154 00:04:33,650 --> 00:04:35,670 level, if you have low B6 levels. 155 00:04:35,670 --> 00:04:36,460 You're not going to convert 156 00:04:36,460 --> 00:04:37,540 well from glutamate to GABA. 157 00:04:39,240 --> 00:04:40,250 This is the GABA receptor. 158 00:04:40,310 --> 00:04:40,850 You don't have to worry 159 00:04:40,850 --> 00:04:41,470 about this too much. 160 00:04:41,470 --> 00:04:42,140 Just to know that it's 161 00:04:42,140 --> 00:04:44,030 a pentameric structure. 162 00:04:44,030 --> 00:04:45,270 It's got five subunits. 163 00:04:45,600 --> 00:04:47,210 And these subunits change depending on 164 00:04:47,210 --> 00:04:49,250 where the GABA receptor is in the brain. 165 00:04:49,510 --> 00:04:51,540 Sometimes they'll look one way and 166 00:04:51,550 --> 00:04:52,480 they'll have various combinations 167 00:04:52,480 --> 00:04:53,540 depending on what they're doing. 168 00:04:53,920 --> 00:04:55,200 GABA is everywhere in the brain. 169 00:04:55,380 --> 00:04:56,890 These GABA receptors, the subunits 170 00:04:57,180 --> 00:04:58,710 change depending on what's required and 171 00:04:58,710 --> 00:05:00,460 what's going on in that particular area. 172 00:05:01,230 --> 00:05:02,110 So this is the mechanism of the 173 00:05:02,110 --> 00:05:03,940 GABA receptor, so we're going 174 00:05:03,940 --> 00:05:04,910 to start with GABA A here. 175 00:05:05,390 --> 00:05:07,120 So you have activation of the receptor, 176 00:05:07,730 --> 00:05:09,030 you have opening of the central pore, 177 00:05:09,450 --> 00:05:11,150 you have influx of chloride, you have 178 00:05:11,150 --> 00:05:13,130 hyperpolarization, you have decreased 179 00:05:13,130 --> 00:05:14,640 occurrence of the action potential. 180 00:05:14,650 --> 00:05:16,100 So this all is saying that you're 181 00:05:16,100 --> 00:05:18,930 inhibiting the actual firing 182 00:05:18,940 --> 00:05:19,950 of this particular neuron 183 00:05:19,960 --> 00:05:21,530 that has the GABA receptor. 184 00:05:21,820 --> 00:05:23,370 So you're inhibiting the action potential. 185 00:05:23,380 --> 00:05:24,370 So you're stopping things, you're 186 00:05:24,370 --> 00:05:25,930 calming things down in general. 187 00:05:26,920 --> 00:05:27,900 Chloride goes through, 188 00:05:28,260 --> 00:05:29,000 and it hyperpolarizes. 189 00:05:30,900 --> 00:05:32,050 This is the GABA B receptor. 190 00:05:32,050 --> 00:05:33,820 It's called a G protein couple receptor. 191 00:05:33,820 --> 00:05:35,330 It's a little bit different, and it's 192 00:05:35,330 --> 00:05:36,710 called a metabotropic receptor, and I'll 193 00:05:36,710 --> 00:05:37,870 show you what this means in a minute. 194 00:05:38,230 --> 00:05:39,000 This is GABA B. 195 00:05:39,000 --> 00:05:41,390 So, GABA B itself, what it does, 196 00:05:41,390 --> 00:05:43,740 it's a presynaptic and postsynaptic. 197 00:05:43,750 --> 00:05:45,380 So, presynaptically, it's preventing, 198 00:05:45,580 --> 00:05:47,180 here, the release of an excitatory 199 00:05:47,520 --> 00:05:48,770 neurotransmitter, glutamate, which is 200 00:05:49,060 --> 00:05:50,090 what we've been talking about before, 201 00:05:50,090 --> 00:05:51,140 is the conversion of glutamate to GABA. 202 00:05:52,110 --> 00:05:53,720 And then you have the postsynaptic, here, 203 00:05:53,720 --> 00:05:56,225 which is increasing potassium outflux, 204 00:05:56,225 --> 00:05:57,745 which causes the hyperpolarization. 205 00:05:57,745 --> 00:05:59,365 It's a little bit different, and 206 00:05:59,375 --> 00:06:00,725 there's a different distribution of 207 00:06:00,725 --> 00:06:01,895 the GABA B receptors in the brain. 208 00:06:03,195 --> 00:06:04,215 So here's a quick summary. 209 00:06:04,215 --> 00:06:07,235 So GABA A is, it's called an ionotropic, 210 00:06:07,235 --> 00:06:08,545 or it's a ligand gated channel 211 00:06:08,615 --> 00:06:10,605 opening, and it's a pentamer structure. 212 00:06:10,865 --> 00:06:13,785 It's widespread as post synaptic influx. 213 00:06:14,055 --> 00:06:16,975 It's endogenous agonist is GABA. 214 00:06:16,975 --> 00:06:18,045 You have other drugs acting on it, 215 00:06:18,065 --> 00:06:19,725 which we'll talk about in a minute. 216 00:06:19,745 --> 00:06:21,875 Pharmacological actions here and then 217 00:06:21,875 --> 00:06:24,300 GABA B is, as you see here, it's 218 00:06:24,300 --> 00:06:26,060 also widespread, it's metabotropic, 219 00:06:26,440 --> 00:06:28,120 it's presynaptic and postsynaptic, 220 00:06:28,610 --> 00:06:30,450 and it has these particular, 221 00:06:30,450 --> 00:06:31,630 pharmacological actions as well, 222 00:06:31,800 --> 00:06:32,060 all right. 223 00:06:32,060 --> 00:06:32,580 So. 224 00:06:33,880 --> 00:06:34,890 There's a couple definitions here. 225 00:06:34,890 --> 00:06:36,860 So orthosteric ligands, these 226 00:06:36,860 --> 00:06:38,160 are chemicals that interact with 227 00:06:38,160 --> 00:06:39,270 the same binding site as the 228 00:06:39,270 --> 00:06:40,810 natural endogenous chemical. 229 00:06:41,110 --> 00:06:41,760 In this case, we're 230 00:06:41,760 --> 00:06:43,520 talking about GABA itself. 231 00:06:44,030 --> 00:06:46,250 So an allosteric ligand or allosteric 232 00:06:46,280 --> 00:06:48,540 modulator is something that works by 233 00:06:48,560 --> 00:06:50,190 modifying how the receptors behave when 234 00:06:50,190 --> 00:06:51,850 it's bound to the orthosteric ligand. 235 00:06:52,150 --> 00:06:52,690 So in this case, we're 236 00:06:52,690 --> 00:06:54,280 talking about a separate site. 237 00:06:54,610 --> 00:06:56,800 away from GABA that binds this 238 00:06:56,810 --> 00:06:59,010 particular modulator and then makes 239 00:06:59,010 --> 00:07:01,500 GABA work better or helps the binding or 240 00:07:01,510 --> 00:07:02,940 improves the chloride channel opening. 241 00:07:03,830 --> 00:07:05,580 And then a positive allosteric modulator 242 00:07:05,900 --> 00:07:07,470 is something that binds and it causes 243 00:07:07,470 --> 00:07:08,920 this positive response where you have 244 00:07:08,920 --> 00:07:10,610 an increased affinity of GABA to bind, 245 00:07:10,870 --> 00:07:12,310 you have more chloride going through, 246 00:07:12,310 --> 00:07:13,610 and you have more hyperpolarization. 247 00:07:13,610 --> 00:07:14,760 So this is a picture of the 248 00:07:14,760 --> 00:07:16,010 GABA receptor and ligand. 249 00:07:16,010 --> 00:07:17,950 So here's a couple, examples of 250 00:07:17,950 --> 00:07:19,500 what it looks like to have where 251 00:07:19,760 --> 00:07:21,800 GABA is binding and where some of 252 00:07:21,800 --> 00:07:24,040 these other drugs will bind to. 253 00:07:24,070 --> 00:07:26,810 So you have alcohol everybody used 254 00:07:26,810 --> 00:07:28,260 to love or maybe still loves alcohol. 255 00:07:28,520 --> 00:07:30,710 It's got a very high affinity 256 00:07:30,720 --> 00:07:32,500 for the GABA receptor. 257 00:07:32,500 --> 00:07:33,340 Very, very high affinity. 258 00:07:33,820 --> 00:07:36,030 Benzodiazepines here, very 259 00:07:36,030 --> 00:07:36,830 high affinity as well. 260 00:07:37,450 --> 00:07:38,940 Has anybody ever used Flamazenil before? 261 00:07:39,360 --> 00:07:40,510 I used it a couple of times in 262 00:07:40,890 --> 00:07:42,040 residency, I don't recommend it. 263 00:07:42,040 --> 00:07:43,040 It causes seizures because 264 00:07:43,040 --> 00:07:44,300 it has the opposite effect. 265 00:07:45,440 --> 00:07:47,180 GABA antagonist, so it prevents 266 00:07:47,520 --> 00:07:48,610 the chloride channel from opening. 267 00:07:49,050 --> 00:07:50,560 Zolpidem, which is the Z drugs, 268 00:07:50,590 --> 00:07:53,220 Ambien and others, they bind and bind 269 00:07:53,220 --> 00:07:54,650 very tightly to the GABA receptor. 270 00:07:55,260 --> 00:07:57,590 Quaaludes, anybody ever tried a Quaalude? 271 00:07:57,770 --> 00:07:58,780 I don't know how everybody, yeah. 272 00:07:59,160 --> 00:07:59,390 Dr. 273 00:07:59,390 --> 00:08:00,440 Ted, no, no. 274 00:08:00,890 --> 00:08:01,900 This is back in the 70s. 275 00:08:02,140 --> 00:08:03,760 So, but they also were, , A GABA 276 00:08:03,760 --> 00:08:05,470 binding here, an allosteric site, 277 00:08:05,860 --> 00:08:07,660 barbiturates, which we use sometimes 278 00:08:07,660 --> 00:08:08,960 for alcohol withdrawal, actually. 279 00:08:09,390 --> 00:08:10,390 Sometimes we'll still use those, 280 00:08:10,400 --> 00:08:11,430 but for pretty much not used 281 00:08:11,430 --> 00:08:13,240 otherwise, general anesthetics. 282 00:08:13,240 --> 00:08:15,010 And then finally, the GABA is 283 00:08:15,010 --> 00:08:16,500 where it's GABA binding itself. 284 00:08:16,500 --> 00:08:17,660 So that's where GABA is binding. 285 00:08:18,120 --> 00:08:19,680 And so all these other sites on the 286 00:08:19,680 --> 00:08:22,220 GABA receptor are places where other 287 00:08:22,220 --> 00:08:25,880 molecules can bind, increase or decrease 288 00:08:25,880 --> 00:08:27,810 the affinity of GABA binding and increase 289 00:08:27,810 --> 00:08:29,540 or decrease chloride channel opening. 290 00:08:29,990 --> 00:08:31,140 It's on the right side 291 00:08:31,140 --> 00:08:32,300 of your screen over there. 292 00:08:32,510 --> 00:08:33,790 You can see just a top view 293 00:08:33,790 --> 00:08:34,650 of the same thing happening. 294 00:08:34,650 --> 00:08:36,520 Benzos are probably the most common 295 00:08:36,760 --> 00:08:38,340 positive allosteric modulator of 296 00:08:38,340 --> 00:08:39,540 the GABA receptor that we use. 297 00:08:39,880 --> 00:08:40,730 Unfortunately, Benzos 298 00:08:40,740 --> 00:08:42,160 have a very high affinity. 299 00:08:42,160 --> 00:08:43,750 We're talking about Ativan, 300 00:08:43,750 --> 00:08:45,810 Xanax, Valium, those kinds of 301 00:08:45,810 --> 00:08:46,890 drugs have a very high affinity. 302 00:08:47,330 --> 00:08:48,540 affinity for the GABA receptor. 303 00:08:48,570 --> 00:08:50,570 So when somebody is taking these 304 00:08:50,580 --> 00:08:52,070 medications for long periods of time, they 305 00:08:52,070 --> 00:08:53,570 cause tolerance, they cause withdrawal, 306 00:08:53,860 --> 00:08:56,570 they can actually cause hallucinations 307 00:08:56,570 --> 00:08:58,060 and death and all those fun things too. 308 00:08:58,080 --> 00:09:00,220 So, but you can see here that what I 309 00:09:00,220 --> 00:09:01,380 wanted to point out is that there's 310 00:09:01,380 --> 00:09:02,430 different subunits of the Alpha 311 00:09:02,430 --> 00:09:04,760 1 subunit of the GABA receptor is 312 00:09:04,760 --> 00:09:06,060 associated with sedation hypnosis. 313 00:09:06,110 --> 00:09:06,930 So this is actually a lot of 314 00:09:06,930 --> 00:09:09,630 your Z drugs, like your Ambien's 315 00:09:09,630 --> 00:09:10,180 and Lunesta's of the world. 316 00:09:10,440 --> 00:09:12,220 And then your Alpha 2 subunit is. 317 00:09:12,290 --> 00:09:13,780 It's more of your anxiolytic 318 00:09:14,100 --> 00:09:15,050 and muscle relaxer. 319 00:09:15,050 --> 00:09:15,970 So this is where your benzo 320 00:09:15,970 --> 00:09:17,080 is going to mostly bind. 321 00:09:17,530 --> 00:09:19,310 So in general, positive allosteric 322 00:09:19,310 --> 00:09:23,010 modulators are less addictive overall. 323 00:09:23,350 --> 00:09:25,080 However, that's not the case obviously 324 00:09:25,080 --> 00:09:27,650 for benzos and barbiturates and alcohol. 325 00:09:28,540 --> 00:09:29,840 And some of the natural equivalents that 326 00:09:29,860 --> 00:09:32,200 we'll talk about do have less of affinity, 327 00:09:32,200 --> 00:09:33,390 but still have significant impact. 328 00:09:34,185 --> 00:09:35,535 So drugs that act on the GABA 329 00:09:35,535 --> 00:09:37,155 B receptor, the most famous 330 00:09:37,155 --> 00:09:39,125 being, GHB gamma hydroxybutyrate. 331 00:09:39,615 --> 00:09:41,455 GHB is well known as the , date rape drug. 332 00:09:41,505 --> 00:09:42,705 But it's actually a fantastic drug 333 00:09:42,705 --> 00:09:45,185 for muscle relaxation, sleep, and 334 00:09:45,185 --> 00:09:47,285 has lots of great other indications, 335 00:09:47,285 --> 00:09:48,455 including narcolepsy actually. 336 00:09:48,455 --> 00:09:50,335 If anybody lives, listens to our podcast, 337 00:09:50,345 --> 00:09:52,445 the Smarter Not Harder podcast, I had a 338 00:09:52,715 --> 00:09:54,195 really great conversation with a guy named 339 00:09:54,195 --> 00:09:56,135 Dan Party, who was involved in getting 340 00:09:56,135 --> 00:09:58,195 GHB to market for pharmaceutical reasons 341 00:09:58,195 --> 00:09:59,985 with very interesting talk with him. 342 00:09:59,985 --> 00:10:03,905 So we're going to switch over here. 343 00:10:03,905 --> 00:10:05,955 So GABA cell GABA in general. 344 00:10:06,500 --> 00:10:08,090 The cells that have GABA receptors 345 00:10:08,090 --> 00:10:09,950 are mostly what we call inter neurons. 346 00:10:10,250 --> 00:10:11,240 These are neurons that are 347 00:10:11,245 --> 00:10:13,310 between neurons, inter neurons, 348 00:10:13,520 --> 00:10:14,600 and they're really important for 349 00:10:14,600 --> 00:10:16,400 learning, for memory, for behavior. 350 00:10:16,640 --> 00:10:17,540 They're kind of like the way 351 00:10:17,540 --> 00:10:19,370 stations between sensory and motor 352 00:10:19,430 --> 00:10:21,440 processing, and even though they're 353 00:10:21,440 --> 00:10:22,670 really small, like if you can't 354 00:10:22,675 --> 00:10:23,990 really see here, but it's a tiny one. 355 00:10:24,410 --> 00:10:25,390 Like, the GABA here, but this is the 356 00:10:25,390 --> 00:10:27,640 big dopamine receptor, , neuron, the big 357 00:10:27,640 --> 00:10:29,410 5 HTP, the big serotonin neuron here. 358 00:10:29,710 --> 00:10:31,240 But you have, like, the small GABA. 359 00:10:31,250 --> 00:10:32,550 This is doing a lot of the 360 00:10:32,550 --> 00:10:33,860 processing between them. 361 00:10:34,170 --> 00:10:35,370 So they're extremely important, and 362 00:10:35,370 --> 00:10:36,860 they're actually in these locations 363 00:10:37,160 --> 00:10:38,720 to make sure that they can actually be 364 00:10:38,720 --> 00:10:40,630 those wave stations to prevent signaling. 365 00:10:41,110 --> 00:10:42,420 Oftentimes, in our brain, it's 366 00:10:42,420 --> 00:10:43,750 actually preventing signaling 367 00:10:43,750 --> 00:10:44,860 that's most important, not 368 00:10:45,200 --> 00:10:47,000 propagating, interestingly enough. 369 00:10:47,000 --> 00:10:47,040 Okay. 370 00:10:48,110 --> 00:10:49,010 So we're going to talk about how 371 00:10:49,010 --> 00:10:50,440 you can dim your GABA switches 372 00:10:50,600 --> 00:10:51,790 without a prescription required. 373 00:10:52,070 --> 00:10:53,700 And, but the first thing to say is 374 00:10:53,710 --> 00:10:55,380 that most GABA supplements don't work. 375 00:10:55,400 --> 00:10:56,930 And we, and I was mentioning that 376 00:10:56,960 --> 00:10:58,090 earlier, it's because GABA is such 377 00:10:58,090 --> 00:10:59,110 a big molecule, it doesn't get 378 00:10:59,110 --> 00:11:00,350 across the blood brain barrier. 379 00:11:01,475 --> 00:11:02,985 If you do have patients that are taking 380 00:11:02,985 --> 00:11:05,145 GABA and they are getting an effect, 381 00:11:05,495 --> 00:11:06,895 it could mean that they have a leaky 382 00:11:06,895 --> 00:11:08,935 brain, leaky gut axis, potentially. 383 00:11:09,365 --> 00:11:11,085 There are some formulations, maybe 384 00:11:11,085 --> 00:11:12,945 nanoliposomal, for example, that may work. 385 00:11:12,975 --> 00:11:14,595 But in general, if they're getting a 386 00:11:14,595 --> 00:11:16,335 significant impact from GABA itself, 387 00:11:16,585 --> 00:11:17,685 at least clinically, I've seen that 388 00:11:17,685 --> 00:11:19,115 they often have a leaky gut, and that 389 00:11:19,115 --> 00:11:21,045 usually means they have a leaky brain. 390 00:11:21,605 --> 00:11:22,335 I don't like telling patients 391 00:11:22,345 --> 00:11:23,245 they have a leaky brain because 392 00:11:23,245 --> 00:11:24,135 that doesn't sound that great. 393 00:11:24,535 --> 00:11:25,795 I usually say that your 394 00:11:25,795 --> 00:11:26,665 blood brain barrier may not 395 00:11:26,665 --> 00:11:28,675 be as great as it should be. 396 00:11:28,675 --> 00:11:29,845 But anyway, so you can also, of 397 00:11:29,845 --> 00:11:32,665 course, give glutamine and glutamates. 398 00:11:32,735 --> 00:11:35,645 So glutamine is an amino acid, it's 399 00:11:35,645 --> 00:11:38,025 in various types of foods, meat, 400 00:11:38,530 --> 00:11:40,700 Spinach, and fish as well, of course. 401 00:11:40,970 --> 00:11:41,950 And so you can get glutamine from a lot 402 00:11:41,950 --> 00:11:43,410 of different sources, but what we do in 403 00:11:43,420 --> 00:11:45,390 health optimization medicine and practice, 404 00:11:45,390 --> 00:11:46,730 we test for these kinds of things. 405 00:11:46,730 --> 00:11:48,540 We test vitamin B6, we test 406 00:11:48,540 --> 00:11:50,030 for magnesium, we test their 407 00:11:50,030 --> 00:11:51,230 glutamine levels, and we can tell. 408 00:11:51,230 --> 00:11:53,450 And if they have a certain symptomatology 409 00:11:53,770 --> 00:11:55,900 and they have certain co factor 410 00:11:55,900 --> 00:11:57,220 deficiencies, well, you know, we know 411 00:11:57,220 --> 00:11:58,570 that they're probably GABA deficient too. 412 00:11:58,570 --> 00:11:59,190 MSG. 413 00:11:59,270 --> 00:12:00,220 Everybody loves MSG. 414 00:12:00,220 --> 00:12:01,790 Everybody actually doesn't love MSG. 415 00:12:01,790 --> 00:12:03,460 It's monosodium glutamate, right? 416 00:12:03,460 --> 00:12:04,070 This is what you can get 417 00:12:04,070 --> 00:12:05,080 in Chinese restaurants. 418 00:12:05,300 --> 00:12:06,440 They make the food nice and sweet 419 00:12:06,440 --> 00:12:07,650 for you, but you get a headache. 420 00:12:07,910 --> 00:12:09,140 That's because you get all of a sudden 421 00:12:09,140 --> 00:12:11,420 this huge rise in glutamate, and you have 422 00:12:11,420 --> 00:12:13,010 to get that conversion over to glutamate, 423 00:12:13,400 --> 00:12:14,980 to GABA, and that can take some time. 424 00:12:16,065 --> 00:12:17,355 And nicotinyl GABA. 425 00:12:17,365 --> 00:12:19,435 So this is a really cool form of 426 00:12:19,435 --> 00:12:21,345 GABA that's attached to a vitamin B3. 427 00:12:21,775 --> 00:12:23,275 And when you do this, you actually 428 00:12:23,285 --> 00:12:24,495 allow this molecule, nicotinyl 429 00:12:24,495 --> 00:12:26,035 GABA, to get through the blood 430 00:12:26,045 --> 00:12:27,285 brain barrier very easily. 431 00:12:27,335 --> 00:12:28,305 And then it hydrolyzes 432 00:12:28,305 --> 00:12:29,605 to vitamin B3 and GABA. 433 00:12:29,625 --> 00:12:31,155 And when that happens, you get this 434 00:12:31,155 --> 00:12:32,605 nice vitamin B3 effect, which is 435 00:12:32,605 --> 00:12:35,175 mild vasodilation and mild energy 436 00:12:35,175 --> 00:12:37,265 production, , At the same time, your 437 00:12:37,275 --> 00:12:39,025 GABA itself, getting into the brain, 438 00:12:39,045 --> 00:12:41,845 increasing, your GABA ability and 439 00:12:41,865 --> 00:12:43,505 increasing GABA binding to its receptor. 440 00:12:43,505 --> 00:12:44,295 So relaxation. 441 00:12:44,295 --> 00:12:45,255 What's nice about this is it's 442 00:12:45,255 --> 00:12:47,015 not very sedating for most people. 443 00:12:47,215 --> 00:12:48,295 So if you have anxiety and stress 444 00:12:48,295 --> 00:12:49,955 during the day, you can take nicotinyl 445 00:12:49,955 --> 00:12:51,915 GABA and you don't feel tired. 446 00:12:51,955 --> 00:12:53,605 You just don't feel stressed, anybody use 447 00:12:53,605 --> 00:12:55,835 valerian root before for patients, right? 448 00:12:55,835 --> 00:12:56,525 So very common. 449 00:12:56,775 --> 00:12:58,075 This is actually a valerian 450 00:12:58,075 --> 00:12:59,045 root, something that actually 451 00:12:59,295 --> 00:13:01,175 binds to the benzo site. 452 00:13:01,245 --> 00:13:03,615 So it's a positive allosteric 453 00:13:04,175 --> 00:13:05,665 modulator of the GABA receptor. 454 00:13:05,665 --> 00:13:07,015 Doesn't bind as tightly, but it does work 455 00:13:07,335 --> 00:13:08,715 really well for some people for sleep. 456 00:13:09,485 --> 00:13:10,285 Covain, which is the 457 00:13:10,285 --> 00:13:11,405 active ingredient in Kava. 458 00:13:11,405 --> 00:13:13,265 It's actually a similar binding site. 459 00:13:13,315 --> 00:13:14,705 Also a positive allosteric 460 00:13:14,725 --> 00:13:16,945 modulator of the GABA receptor. 461 00:13:16,945 --> 00:13:17,905 Honokyl. 462 00:13:17,905 --> 00:13:19,295 Anybody used Honokyl as well? 463 00:13:19,695 --> 00:13:21,175 So this is from Magnolia Bark. 464 00:13:21,495 --> 00:13:23,115 Also binds as a positive allosteric 465 00:13:23,125 --> 00:13:25,245 modulator to the GABA receptor. 466 00:13:25,245 --> 00:13:27,045 Works really well, for a lot of people. 467 00:13:27,045 --> 00:13:28,065 Does anybody know what this is? 468 00:13:30,245 --> 00:13:31,145 It's a mushroom it's a 469 00:13:31,145 --> 00:13:32,055 very famous mushroom. 470 00:13:32,085 --> 00:13:33,565 It's called Flyagaric, or 471 00:13:34,165 --> 00:13:35,845 Amanita muscaria is the other 472 00:13:35,845 --> 00:13:38,775 name for it, of Christmas lore. 473 00:13:38,775 --> 00:13:39,445 Does anybody know about the 474 00:13:39,445 --> 00:13:41,355 Christmas tales of Amanita? 475 00:13:41,405 --> 00:13:44,260 Amanita has two compounds in it, mostly. 476 00:13:44,260 --> 00:13:44,910 It's got a lot of other 477 00:13:44,910 --> 00:13:45,990 things, but two major ones. 478 00:13:46,360 --> 00:13:48,460 One is called agarin, otherwise 479 00:13:48,460 --> 00:13:50,170 named muscimol, and another 480 00:13:50,170 --> 00:13:51,590 one is called ibotenic acid. 481 00:13:52,200 --> 00:13:53,760 Ibotenic acid is neurotoxic. 482 00:13:54,090 --> 00:13:55,510 This is the one that mostly causes 483 00:13:55,530 --> 00:13:57,850 the psychedelic experiences of 484 00:13:57,850 --> 00:13:58,950 taking this particular mushroom. 485 00:13:59,660 --> 00:14:00,910 But, you don't mostly take 486 00:14:00,910 --> 00:14:01,930 this mushroom directly. 487 00:14:02,380 --> 00:14:04,950 The stories were that shamans would 488 00:14:04,960 --> 00:14:08,030 drink the urine of reindeers, because 489 00:14:08,030 --> 00:14:10,340 reindeers would be able to tolerate this. 490 00:14:10,340 --> 00:14:10,740 Okay. 491 00:14:10,990 --> 00:14:11,750 And then the shaman would 492 00:14:11,750 --> 00:14:13,380 actually then urinate. 493 00:14:13,480 --> 00:14:14,180 And then other people 494 00:14:14,180 --> 00:14:14,980 would drink the urine. 495 00:14:15,350 --> 00:14:16,530 This is in Northern. 496 00:14:17,140 --> 00:14:18,250 You can, this is actually a great New 497 00:14:18,250 --> 00:14:19,400 York times article on this with some 498 00:14:19,400 --> 00:14:21,280 great videos as well, but that's mostly 499 00:14:21,280 --> 00:14:22,550 because the toxicity is because of 500 00:14:22,550 --> 00:14:25,380 ibotenic acid, but agarin or muscimol 501 00:14:25,380 --> 00:14:28,810 is a fantastic orthosteric ligand of 502 00:14:28,810 --> 00:14:31,305 the GABA receptor, which means That it 503 00:14:31,305 --> 00:14:33,555 directly enhances GABA in the system, 504 00:14:33,705 --> 00:14:35,085 and it does it very effectively. 505 00:14:35,385 --> 00:14:36,525 But the key is to have 506 00:14:36,525 --> 00:14:37,695 it at very low doses. 507 00:14:38,055 --> 00:14:39,435 So it's a GABA receptor agonist. 508 00:14:39,435 --> 00:14:41,025 It easily crosses the blood-brain barrier. 509 00:14:41,355 --> 00:14:42,885 It's got a high potency, it's long-acting. 510 00:14:42,935 --> 00:14:44,615 It's about 6 to 10 hours 511 00:14:44,645 --> 00:14:45,995 overall for a half-life. 512 00:14:46,395 --> 00:14:47,475 It's naturally occurring, or you can 513 00:14:47,475 --> 00:14:49,285 make it synthetically, in low doses. 514 00:14:49,285 --> 00:14:50,365 It's safe and effective. 515 00:14:50,665 --> 00:14:52,015 And at high doses it can be 516 00:14:52,015 --> 00:14:53,185 hallucinogenic, but usually in, 517 00:14:53,185 --> 00:14:54,805 in combination with the Ibotenic 518 00:14:54,825 --> 00:14:55,945 acid and the actual musher. 519 00:14:56,600 --> 00:14:58,890 Non pharmacologic, of course, yoga, 520 00:14:59,100 --> 00:15:00,490 meditation, breathwork, anything 521 00:15:00,490 --> 00:15:01,160 that's going to make you more 522 00:15:01,170 --> 00:15:02,820 parasympathetic is also going to 523 00:15:02,820 --> 00:15:04,220 increase GABA tone in the brain. 524 00:15:05,660 --> 00:15:07,500 Physical activity also helps reset the 525 00:15:07,500 --> 00:15:08,760 system and the balance between glutamate 526 00:15:08,760 --> 00:15:10,920 and GABA, so also being physically 527 00:15:10,950 --> 00:15:12,270 active is also really important. 528 00:15:13,210 --> 00:15:14,810 And then, finally, it's really 529 00:15:14,810 --> 00:15:16,650 important, and this is kind of the 530 00:15:16,650 --> 00:15:18,210 ethos of health optimization medicine 531 00:15:18,210 --> 00:15:20,050 and practice, is we're detecting and 532 00:15:20,050 --> 00:15:22,010 correcting at the metabolomic level. 533 00:15:22,010 --> 00:15:22,860 And so, you really want to be 534 00:15:22,960 --> 00:15:25,240 keeping the GABA deficiency aspect 535 00:15:25,240 --> 00:15:26,550 of things on your clinical radar. 536 00:15:27,150 --> 00:15:28,440 So we test for the nutrients. 537 00:15:28,440 --> 00:15:29,270 We test for magnesium. 538 00:15:29,270 --> 00:15:30,340 We test for vitamin B6. 539 00:15:30,650 --> 00:15:32,900 We ensure optimized GABA production. 540 00:15:33,220 --> 00:15:35,160 And you want to do that as sort 541 00:15:35,160 --> 00:15:36,440 of your baseline for everybody. 542 00:15:36,440 --> 00:15:37,950 So when somebody comes to see me, I'm 543 00:15:37,950 --> 00:15:40,230 not looking for GABA deficiency exactly. 544 00:15:40,230 --> 00:15:41,280 What I'm doing is doing a full 545 00:15:41,280 --> 00:15:43,350 metabolic, metabolomic profile, 546 00:15:43,940 --> 00:15:46,980 correcting as I see, and then you often 547 00:15:46,980 --> 00:15:48,770 will see these improvements in mood 548 00:15:48,770 --> 00:15:50,170 and depression and anxiety because 549 00:15:50,170 --> 00:15:51,190 you're actually working on that. 550 00:15:51,635 --> 00:15:52,615 neurotransmitter system. 551 00:15:52,935 --> 00:15:54,765 Sometimes you can give herbals 552 00:15:54,815 --> 00:15:55,905 and you can give supplements and 553 00:15:55,905 --> 00:15:57,215 things like that to help right now. 554 00:15:57,555 --> 00:15:58,485 That's what the company, the 555 00:15:58,695 --> 00:15:59,785 transcriptions company is all about. 556 00:15:59,785 --> 00:16:01,685 But the key for the long term is to really 557 00:16:02,335 --> 00:16:04,305 work on that foundation and optimize it. 558 00:16:04,305 --> 00:16:05,675 Of course, you want to implement dietary 559 00:16:05,675 --> 00:16:07,025 and lifestyle measures to boost GABA 560 00:16:07,025 --> 00:16:09,505 production, considering herbal and fungal 561 00:16:09,505 --> 00:16:11,385 GABA agonists and orthosteric ligands 562 00:16:11,385 --> 00:16:12,675 to support GABA production as well. 563 00:16:13,295 --> 00:16:14,085 And then you want to really want to 564 00:16:14,095 --> 00:16:17,000 avoid your benzos and your barbiturates, 565 00:16:17,000 --> 00:16:19,060 obviously, and drugs that are going to 566 00:16:19,070 --> 00:16:20,650 cause dependence, withdrawal, intolerance. 567 00:16:20,650 --> 00:16:22,680 I mean, that's just important 568 00:16:22,710 --> 00:16:23,540 for us to think about. 569 00:16:23,910 --> 00:16:25,540 Sometimes it's unavoidable and I use 570 00:16:25,540 --> 00:16:26,540 these in my patients when they really 571 00:16:26,540 --> 00:16:28,010 need it, but oftentimes we can get 572 00:16:28,010 --> 00:16:29,320 away with not using them because we 573 00:16:29,320 --> 00:16:31,180 have a lot of great options here from 574 00:16:31,180 --> 00:16:32,650 an herbal and fungal perspective. 575 00:16:34,570 --> 00:16:35,930 Thank you guys very much for listening. 576 00:16:36,100 --> 00:16:37,080 I really appreciate your time.