![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by Rick on November 6, 2001, at 19:16:24
aka: Pharmacology/Shmarmacology
aka: Hey, whatever works...
-------------
NOTE: THIS IS RATHER LONG. YOU CAN SKIP THE PARAGRAPHS MARKED [CAN SKIP] FOR A CONDENSED VERSION.
-------------As I’ve posted ad nauseum, I’ve had great, consistent success with my cocktail of Klonopin, Serzone and the novel, non-amphetamine, psychoactive stimulant Provigil (modafinil) for severe non-depressive Social Anxiety. And my doses have never gone up, only down.
Today I had vivid reinforcement of what a powerful contributor Provigil is to my treatment!
[CAN SKIP] Background: Because of concern over the bothersome benign floaters (hair-like and round, usually-opaque-appearing “debris” floating in my left eye’s field of vision under many condtions), I decided to stop the Provigil awhile on the slim chance that it could be potentiating my awareness of these cursed swirling dervishes of bound protein. (The floaters started showing up within a few months of the time I added Serzone and Provigil to the Klonopin I had been taking for over a year. One study shows a pre-optic region of the brain to be one of the main areas where Provigil increases alertness. Incidentally, as I mentioned in another thread, Serzone is notorious among AD’s for affecting visual perception.)
Well, I had long ago reduced my daily Klonopin to 1 mg since being on the cocktail. And while I still WASN’T getting fatigued after experimentally stopping the Provigil three days ago (even though Serzone and Klonopin can both be sedating ) I DID find myself getting more anxious. Still 50-60% better than pre-Klonopin, but I’ve been used to 80-90% since taking the cocktail. I take all my meds in the morning. But late this morning, as I found my voice getting a little shaky during an important conference call, so I added a mere .25 mg of Klonopin. Within 15 minutes, I could barely keep my eyes open. So I violated my no-Provigil experiment and took 100 mg (my usual daily dose) from my pocket pill holder. Withon a half hour, I was more awake, but still sleepy. So I impatiently took another 100 mg, since I occasionally take 200 mg in one day, (Doubling my Provigil dosage provides a nice added boost for a day or two, but then starts getting me a bit wired.) By the time the terminally-dull conference call was over, I was fully awake.
Later today, I was in a meeting and noticed that I was asserting myself so confidently, with great energy -- a 180-degree turnaround from the way things were in the “old days”. So I told myself, “hey, see, you don’t need Provigil to build energy and confidence.” Of course, moments later I remembered that I HAD violated the floater experiment by taking Provigil 5 hours earlier.
[CAN SKIP] (Aside re briefly forgetting I took the Provigil: the one troublesome aspect of my cocktail – assuming the vitreous floaters AREN’T med-related -- is some memory lapses, so my brief forgetfullness here wasn’t surprising. I can reason and come up with creative ideas better than ever, but will sometimes think, “now WHAT was it I did awhile back regarding this issue?”. The forgetfulness most likely comes from the other meds and perhaps age-related memory loss. Despite the amnesic reputation of benzos, this issue didn’t surface until I began Serzone.)
In any event, this episode just drove home what a greatly beneficial anti-anxiety, assertiveness effect Provigil adds to my social phobia treatment. For me, this novel stimulant is GREAT for anxiety. It was such a pleasant surprise after my disappointment using selegiline and Wellbutrin used as mild stimulants (I refused my pdoc’s desire that I take Ritalin, and convinced him into letting me be his guinea pig for Provigil).
[CAN SKIP ENTIRE SECTION] In all fairness, I have some caveats, although none change my enthusiasm over Provigil’s benefits:
(1) Without Provigil, I likely would have developed more fatigue tolerance to an increased dose of Klonopin within a week or two, as I did when I first took the med. I was, frankly, a little surprised to find that 300 mg Serzone + 1 mg Klonopin wasn’t tiring me out at all w/o Provigi. I’m also surprised that adding a mere .25 mg Klonopin to the usual 1.0 caused so much fatigue. However, I probably shouldn’t be surprised, because I long ago posted on this very board that taking more than 1 mg of Klonopin at a time always makes me sleepy, especially if taken in multiple doses less than four hours apart.
(2) Maybe the initial partial return of anxiety would have largely gone away as my body adjusted to not having Provigil – but I highly doubt it.
(3) I don’t know whether Provigil would work so wonderfully without the other two meds. I sometimes wonder if Serzone's contribution is primarly through metabolic interactions that prolong and intensify the effects of Provigil and Klonopin. But I DO palpably FEEL the Serzone (in a helpful way) when I first take it, and I doubt it could simply be affecting the other meds THAT quickly.
(4) Many users posting to this board have given negative assessments of Provigil. This should by no means be discounted, although I think the reaction can vary greatly according to condition; dosing (recall that 3 days at 200mg makes me wired, even though one or two days is great); kind of combo (Provigil not usually taken solo); mistaking loss of euphoria side-effect as poop-out; confusion with amphetamine-based stims (reflected either as reluctance to take/prescribe OR as an insufficient-effectiveness conclusion by previous (e.g.) Ritalin users – like trying to give BuSpar to a Xanax veteran); or simply expectations out of synch with the drug’s areas of strength.
(5) I went to bed very late last night. Fatigue does make me more prone to anxiety. So maybe the wakefulness-inducing Provigil is especially helpful on days like today. But again, I WASN’T tired this morning until I took that extra little .25 mg of Klonopin. But I don’t recall the time of peak action for Serzone, and certainly don’t know what it would be for possibly-potentiated Klonopin.
(6) While I wasn’t tired at all the previous 3 days sans Provigil (all low-sleep days, too), perhaps there was still some Provigil in my bloodstream.Despite these caveats, today’s episode just reinforces for me what a godsend Provigil is for my Social Phobia, at least in combo with the other meds.
I heard today that importer Cephalon announced record earnings this year based on Provigil. This is despite the failure to show clinical significance in the initial placebo-controlled ADD trial, which had been deemed a major blow to the company. (This may have been related to the way the study was done; I’ve heard they’re continuing to test for this indication based on some very favorable anecdotal evidence.) If they can do this well despite the ADD setback, it’s clear that off-label uses of this med must be exploding, and patients must be responding. (How else could such a high-priced drug drum enough usage to drive up earnings? Certainly not from the relatively small number of people with narcolepsy, the official indication). Unfortunately, I have a feeling anxiety disorders won’t be among any of of the investigated uses anytime soon. (Although benefits in this area may surface as use of Provigil for AD augmentation accelerates, given that AD’s are often prescribed for non-depressive anxiety.) Right now some of the possible focus areas seem to be AD Augmentation, ADD/ADHD. Sleep Apnea, Parkinson’s, and Alzheimer's (not sure if the latter is still under active consideration), and Multiple Sclerosis-induced fatigue (looks very promising here).
Rick
Posted by Mitch on November 7, 2001, at 9:57:23
In reply to Vivid Evidence of Provigil Anti-Anxiety Effects, posted by Rick on November 6, 2001, at 19:16:24
> Despite these caveats, today’s episode just reinforces for me what a godsend Provigil is for my Social Phobia, at least in combo with the other meds.
>
> I heard today that importer Cephalon announced record earnings this year based on Provigil. This is despite the failure to show clinical significance in the initial placebo-controlled ADD trial, which had been deemed a major blow to the company. (This may have been related to the way the study was done; I’ve heard they’re continuing to test for this indication based on some very favorable anecdotal evidence.) If they can do this well despite the ADD setback, it’s clear that off-label uses of this med must be exploding, and patients must be responding. (How else could such a high-priced drug drum enough usage to drive up earnings? Certainly not from the relatively small number of people with narcolepsy, the official indication). Unfortunately, I have a feeling anxiety disorders won’t be among any of of the investigated uses anytime soon. (Although benefits in this area may surface as use of Provigil for AD augmentation accelerates, given that AD’s are often prescribed for non-depressive anxiety.) Right now some of the possible focus areas seem to be AD Augmentation, ADD/ADHD. Sleep Apnea, Parkinson’s, and Alzheimer's (not sure if the latter is still under active consideration), and Multiple Sclerosis-induced fatigue (looks very promising here).
>
> RickRick,
Interesting discussion there about Provigil. I have mixed social anxst and attention problems. I notice that a lot of episodes of social anxiety happen at work when I am 'surprised' by a conference call. NOBODY tells me diddly-squat about it, of course-the phone just rings and there are half a dozen others on the other end sitting around a speaker-phone God knows where. One of those events happened just last week and I had to shift gears suddenly and try to remember what the hell they were trying to ask me...I just paused started to hem/haw and then I felt the panic starting to hit me. Finally, I just told them to summarize what the hell they were wanting, from who, and for what reason and send that to me in an email and then I would get back to them! Our salesperson involved was pissed, but I had to get out of that, my head was just mush. I wonder if a lot of social anxiety I experience is directly related to ADHD symptoms?
Anyhow, isn't Provigil an adrenoreceptor *agonist*?? Also, what role could it play in Parkinson's? I have seen posts about it, but most seemed to be thumbs-down stuff in relation to successful AD augmentation for TRD. What are the most common side-effects?
Mitch
Posted by Rick on November 8, 2001, at 0:42:30
In reply to Vivid Evidence of Provigil Anti-Anxiety Effects, posted by Rick on November 6, 2001, at 19:16:24
>I notice that a lot of episodes of social anxiety happen at work when I am 'surprised' by a conference call. NOBODY tells me diddly-squat about it, of course-the phone just rings and there are half a dozen others on the other end sitting around a speaker-phone God knows where. One of those events happened just last week and I had to shift gears suddenly and try to remember what the hell they were trying to ask me...I just paused started to hem/haw and then I felt the panic starting to hit me. Finally, I just told them to summarize what the hell they were wanting, from who, and for what reason and send that to me in an email and then I would get back to them! Our salesperson involved was pissed, but I had to get out of that, my head was just mush.
I’ve been there! For me, though, the inability to remember was usually a social phobic reaction to being put on the spot. I used to start to panic, too. Now, I stay calm and can think more clearly. And even when some fuzziness remains I’m able to project confidence and even B.S. a little if I need to. While I still care what others think, I don’t obsess over it and let it thrust me into that awful downward spiral. Ironically, some of the “drawing a blank” that used to come from being put on the spot now comes from periodic, temporary memory lapses that may be caused by the Serzone or Klonopin. But overall, the way I react mentally and outwardly in such a situation is night-and-day compared to before. I don’t feel like I’m losing control anymore. I still have some degree of insecurity sometimes, but so do most people.
>I wonder if a lot of social anxiety I experience is directly related to ADHD symptoms?
It very well could be. Anything that (however irrationally) makes you feel deficient or scrutinized in the eyes of others can lead you in that direction if you’re mentally susceptible.
>Anyhow, isn't Provigil an adrenoreceptor *agonist*?? Also, what role could it play in Parkinson's? I have seen posts about it, but most seemed to be thumbs-down stuff in relation to successful AD augmentation for TRD. What are the most common side-effects?
While there’s some debate over certain aspects of how modafinil works (and more agreement in other respects), the initial thought that it acted as an adrenoreceptor agonist seems to have been abandoned. While others on this board may disagree, Provigil seems to have very few side effects. For me, the only side effect seems to be that if I take too much – meaning going more than two days at 200 mg vs. my usual dose of 100 mg, I get a little wired, which can be a little irritating and also cause some of my somatic SP symptoms to return a bit. E.g, I might still very confident, but my voice could start getting a little shaky when I get angry. But this rarely happens, because I watch my dose. (100 mg for me might be equivalent to a higher dose due to Serzone’s enzyme-system-driven potentiation of modafinil). A few other minor side effects MAY be caused partially by Provigil, but they could very well be caused by (or additive with) the Serzone instead (I started them together): mild dry mouth and a harder time getting out of bed than when I was taking Klonopin alone or in various other combos. According to the manufacturer – obviously NOT an unprejudiced source – side effects are uncommon, but the most common seem to be nervousness, headache and insomnia. (I have a have a hard time understanding the last one. While Provigil keeps me awake and alert, I have no trouble sleeping soundly when I want, whether it’s 11 Am. or 11 p.m. And I used to be an insomniac. (Of course, I’m taking Serzone and Klonopin, too. But I’ve seen many people – and of course studies -- cite the same benefit.)
As for some of the less-than-rave reviews here, I have several comments about that which I’ve already made in recent posts (e.g., see mine and a new Provigil user’s comments in the thread “Stimulants, How Do You Get Them?” further down the page). I will mention that one good thing about Provigil from a practical standpoint is that you should know within a few weeks – certainly no more than three weeks – whether it’s going to help you. Like the poster below, I felt distinct benefits the first day. I started with 200 mg and later pared back to 100 with occasional spikes to 200. I may be repeating myself, but I think some people mistake loss of an early mild-euphoria side effect as poop-out. Also, Provigil can eventually cause its own metabolism, which can also be mistaken for poop-out. Instead, it just means you need a TEMPORARY dose increase.
I’ve attached the text of a fairly good summary of the current thought on Provigil pharmacology, from Medscape. As I said, there are still some areas of debate on modafinil’s mechanisms of action, as a recent thread on this board attests.
BTW, Provigil can apparently actually inhibit GABA, but this seems to be limited to specific areas of the brain, and at specific dose levels. In my own experience, Provigil certainly doesn’t appear to have any negative impact on Klonopin’s social anxiety benefits. To the contrary, they seem synergistic. If you’d like to see more about modafinil and GABA (and Glutamate), search on these terms in Medline.
MODAFINIL ORAL
Pharmacology & Chemistry
Description from AHFS DI™
Modafinil, a benzhydryl sulfinylacetamide derivative, is a CNS stimulant that is structurally and pharmacologically distinct from other currently available CNS stimulants (e.g., amphetamines, caffeine, cocaine, methylphenidate). Modafinil promotes vigilance and wakefulness and decreases the number of daytime sleep episodes associated with narcolepsy. Although the wakefulness-promoting effects of modafinil are comparable to those exhibited by amphetamines or methylphenidate, modafinil alters metabolic activity and increases neuronal activity in specific areas of the brain that control sleep/wakefulness and the biologic clock while amphetamines increase neuronal activity more widely throughout the brain, suggesting distinct mechanisms for modafinil and relatively high selectivity.The exact mechanism(s) of action of modafinil is unknown, but animal studies have shown that the drug inhibits the release of Gamma-aminobutyric acid (GABA) and increases the release of glutamate from the cerebral cortex, hippocampus, nucleus acumbens, medial preoptic area, and posterior hypothalamus. GABA is an inhibitory neurotransmitter that acts as a CNS depressant while glutamate is an excitatory neurotransmitter. Modafinil does not appear to be an indirect- or direct-acting dopamine-receptor agonist nor to act as a sympathomimetic agent. Haloperidol, a dopamine-receptor antagonist, inhibits the activity of amphetamine but not the activity of modafinil.
The manufacturer states that modafinil does not appear to be a direct or indirect alpha1-adrenergic agonist, as evidenced by lack of activity in assay systems known to be responsive to such agonists. However, the drug’s stimulant effects (e.g., on wakefulness, locomotion, and the EEG) are antagonized by alpha1-antagonists (e.g., prazosin, phenoxybenzamine), thus indicating that an intact central alpha1-adrenergic system is necessary for modafanil’s CNS activity. In addition, it has been suggested that the drug itself may stimulate central alpha1-adrenergic activity (e.g., at the postsynaptic level). Modafinil does not appear to exhibit clinically important peripheral adrenergic activity, even at high doses. In animals, modafinil increased locomotor activity but didnot increase dopamine activity; however, in vitro studies showed that modafinil binds to dopamine reuptake sites and increases extracellular dopamine concentrations.
At usual pharmacologic concentrations, modafinil does not bind to certain norepinephrine, serotonin, dopamine, GABA, adenosine, histamine H3, melatonin, or benzodiazepine receptors that regulate sleep and wakefulness. The drug also does not inhibit type B monoamine oxidase (MAO-B) or phosphodiesterase and does not alter plasma melatonin or cortisol hormone profiles, which may limit short-term adverse effects. Modafinil does not decrease the incidence of cataplexy in dogs. Although the effects, ifany, of modafinil on blood pressure during long-term therapy remain to be elucidated, 300 mg (200 mg before breakfast and 100 mg before lunch) given on a single day in normotensive patients with obstructive sleep apnea did not appear to substantially affect blood pressure, although increases were noted relative to placebo under mental and physical stress tests.
Like other CNS stimulants, modafinil is reinforcing in animals and produces psychoactive (e.g., alterations in mood and thinking), euphoric, and subjective effects typical of classic psychomotor stimulants (e.g., amphetamines) in humans. Despite this pharmacologic similarity to such stimulants, the chemical properties of modafinil (e.g., not water soluble, decomposes in heat) may limit its abuse potential. In addition, there are substantial relative potency differences between modafinil and CNS stimulants that are subject to control under the Federal Controlled Substances Act as schedule II drugs. These differences reduce the likelihood that modafinil could be abused by the parenteral, intranasal, or inhalation route, as are cocaine, methylphenidate, and amphetamine; therefore, modafinil is subject to control as a schedule IV rather than II drug.
With chronic dosing, modafinil induces its own metabolism via induction of the cytochrome P-450 (CYP) isoenzyme 3A4. Clearance of modafinil may be altered by other inducers (e.g. phenobarbital, carbamazepine, rifampin) or inhibitors (e.g. ketoconazole, itraconazole) of this isoenzyme. (See Drug Interactions.) Inhibition of the CYP isoenzymes 2C9 and 2C19 by modafinil results in several potential drug interactions (e.g. warfarin, phenytoin, diazepam, propranolol, clomipramine, desipramine). (See Drug Interactions.)
General from AHFS DI™
Administration
Modafinil usually is administered orally once daily in the morning. The drug also has been administered in 2 divided doses daily, in the morning and at noon.
Although administration with food can delay GI absorption of modafinil by approximately 30 minutes, food does not affect the extent of absorption and the drug can be administered without regard to meals.
Dosage
The usual recommended dosage of modafinil to improve wakefulness in adults and adolescents 16 years of age and older with excessive daytime sleepiness associated with narcolepsy is 200 mg daily. Although a dosage of 400 mg daily has been well tolerated, there is no consistent evidence indicating that this dosage provides additional clinical benefit beyond that provided by the 200-mg daily dosage.
----------------------------------------------------------
-- Re your Pakinson’s question, here’s one of the lab studies suggestive of Provigil’s potential value for Parkinson’s, but tests on humans have been mainly to show anti-fatigue benefits. I’m guessing Cephalon may not put much effeort against Provigil for Parkinson’s, since they’re working on a novel potential-breakthrough medication specifically targeting this disease.
Posted by Mitch on November 8, 2001, at 9:39:23
In reply to Re: Vivid Evidence of Provigil Anti-Anxiety Effects » Rick, posted by Rick on November 8, 2001, at 0:42:30
Rick,
Thanks for the information! It sounds like it might be effective for my attentional troubles, however I wonder why you are finding it anxiolytic given its putative mechanisms of action? The inhibition of GABA and boost in glutamate makes me a little concerned that it could cause a much lowered seizure threshold and possibly trigger panic. Did you have situational full-blown panic attacks with your SP? If so, and the Provigil seems to *help* that makes me wonder about the difference between "free-floating" versus "situational" panic. I think I read something here weeks ago that talked about a "coffee" test for panic. The poster mentioned that coffee is rarely tolerated by people with "free-floating" panic, while it seems to reduce anxiety/panic in SP folks.
As to the inattentiveness question in relation to SP. I agree that a lot of social anxiety (being put on the spot) has the ability to whack your ability to focus making snowball and get worse. But, I remember when I was taking Adderall, I could be put on the spot and stay "on track" despite being anxious. I really think the ADD contributes a lot to the problems. My analogy here is a record that has "weak grooves" or a record player with a "weak needle". It seems to take very little stimulus to knock me off track (not just being under pressure to perform). I can be at work trying to figure something complex out on paper/computer and people can be talking at the other end of the room, a cell phone goes off, the paging systems becomes active, all sorts of stuff not directed towards me personally, and I can get totally wiped out and have to start over, etc. The panicky part is when the distractions *are* directed toward me.
Mitch
Posted by Rick on November 9, 2001, at 3:36:51
In reply to Re: Vivid Evidence of Provigil Anti-Anxiety Effects » Rick, posted by Mitch on November 8, 2001, at 9:39:23
Mitch --
I can understand your concern with taking anything you believe might have the potential to increase panic attacks. If I were you, I’d really want to know if others with PD – not just any anxiety disorder -- had used Provigil (with a known anxiolytic), and how they fared. (Although I have noticed that, with a few notable exceptions, whatever works for panic seems to be good for social phobia, and vice versa.)
Let me start by responding to your questions about the GABA-inhibition issue first, then I'll get to the rest.
At least acording to the manufacturer, Provigil’s action is primarily (though not exlusively) in the *anterior* hypothalamus and the caudate, two areas which are not thought to be core to panic. (Most of what I’ve read implicates the limbic system and the amygdala as the key regions in panic.) This is in distiction to amphetamine, where the increases in glucose utilization are widespread in the brain. (BTW, the *lower* portion of the caudate is implicated in OCD – maybe that’s why I’m seeing NO reuction in my OCD tendencies??) The anterior hypothalamus is indeed important in regulation of wakefulness and circadian rhythms, thus acounting for much of Provigil’s efficacy. BTW, the study looking for GABA effects from Provigil in these regions found none, concluding that the wakefulness enhancement was due to glutamate enhancement.
The remaining rodent-brain studies reached conflicting conclusions about the ability of modafinil to inhibit GABA in areas of the brain where the med is less concentrated. While results by study/brain region vary from direct GABA inhibition to (theorized) indirect inhibition to no inhibition, I notice that even the “small” doses – the ones that were less likely to show a GABA effect -- were the equivalent of 30 to 100 times the Provigil dosage I take per kg of body weight. And in the one abstract where the GABA reduction was quantified, it was about 15% -- at 300 times my dosage per kg -- in select portions of the basal ganglia.
Maybe I’m missing something, but with a possible 15% GABA reduction, at a ridiculously high dosage, in a brain region that isn’t core to anxiety, I tend not to be too concerned about any anti-GABA effects causing anxiety or diminishing the effectiveness of my Klonopin or Serzone.
Perhaps taking even a small risk lightly is cavalier when the idea is to avoid doing anything that might trigger severe panic, but for me – and a big YMMV here – the key finding is that Provigil greatly enhances my Klonopin/Serzone social phobia treatment. That’s why I subtitled my original post “Pharmacology/Shmarmacology” and “Hey, Whatever Works.”
Now, as far as your other (related) questions...I‘ve had one full-blown panic attack, and a few instances where I was teetering precariously on the edge but started regaining control just in time, e.g., just before bolting from a room full of people waiting for me to present. All of the episodes were situational. One occurred when I was on solo selegiline, one was when I was on solo Nardil (post poop-out), and two were pre-meds (and led to my seeking treatment). There was another time when I went to the emergency room thinking I might be having a heart attack due to persistent chest pains, but I was calm and knew there was probably another cause. I was just being cautious, don’t think it was panic. In retrospect, I think it was gallstone pain lasting a lot longer than usual. In fact, including this episode here is probably superfluous, but I'll leave it anyway.
I've heard of the coffee test, too but I never heard that it was said to *help* social phobics --just that it doesn't cause anxiety. But caffeine DOES negatively affect my treatment enough that I avoid it, although not scrupulously. I drink plenty of caffeinated coffee on the weekend. (BTW, that's when I allow myself free rein to EAT whatever I want, too. I think weight loss has definitely contributed to my treatment.) In any event, I'm sure the cofffee test for panic refers to a MUCH greater increase in anxiety than I experience.
Rick>It sounds like it might be effective for my attentional troubles, however I wonder why you are finding it anxiolytic given its putative mechanisms of action? The inhibition of GABA and boost in glutamate makes me a little concerned that it could cause a much lowered seizure threshold and possibly trigger panic. Did you have situational full-blown panic attacks with your SP? If so, and the Provigil seems to *help* that makes me wonder about the difference between "free-floating" versus "situational" panic. I think I read something here weeks ago that talked about a "coffee" test for panic. The poster mentioned that coffee is rarely tolerated by people with "free-floating" panic, while it seems to reduce anxiety/panic in SP folks.
Posted by Mitch on November 9, 2001, at 9:11:33
In reply to Re: Vivid Evidence of Provigil Anti-Anxiety Effects » Mitch, posted by Rick on November 9, 2001, at 3:36:51
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
[email protected]
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.